chr16-1519931-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_014714.4(IFT140):c.3990G>A(p.Ala1330Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,600,638 control chromosomes in the GnomAD database, including 53 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 12 hom., cov: 33)

Exomes 𝑓: 0.0048 ( 41 hom. )

Consequence

IFT140
NM_014714.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -5.37

Publications

1 publications found

Variant links:

Genes affected

IFT140 (HGNC:29077): (intraflagellar transport 140) This gene encodes one of the subunits of the intraflagellar transport (IFT) complex A. Intraflagellar transport is involved in the genesis, resorption and signaling of primary cilia. The primary cilium is a microtubule-based sensory organelle at the surface of most quiescent mammalian cells, that receives signals from its environment, such as the flow of fluid, light or odors, and transduces those signals to the nucleus. Loss of the corresponding protein in mouse results in renal cystic disease. [provided by RefSeq, Jun 2012]

IFT140 Gene-Disease associations (from GenCC):

autosomal dominant polycystic kidney disease
Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
IFT140-related recessive ciliopathy
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen, Illumina
short-rib thoracic dysplasia 9 with or without polydactyly
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
retinitis pigmentosa 80
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Leber congenital amaurosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Jeune syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

IFT140 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-1519931-C-T is Benign according to our data. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1519931-C-T is described in CliVar as Benign. Clinvar id is 317993.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.37 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0108 (1650/152388) while in subpopulation AFR AF = 0.028 (1166/41592). AF 95% confidence interval is 0.0267. There are 12 homozygotes in GnomAd4. There are 771 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 12 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT140	NM_014714.4 link	c.3990G>A	p.Ala1330Ala	synonymous_variant	Exon 29 of 31	ENST00000426508.7	NP_055529.2	Q96RY7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IFT140	ENST00000426508.7 link	c.3990G>A	p.Ala1330Ala	synonymous_variant	Exon 29 of 31	5	NM_014714.4	ENSP00000406012.2		Q96RY7-1

Frequencies

GnomAD3 genomes

AF:

0.0108

AC:

1647

AN:

152270

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0280

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.00490

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00868

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00454

Gnomad OTH

AF:

0.0110

GnomAD2 exomes

AF:

0.00535

AC:

1279

AN:

239078

AF XY:

0.00525

show subpopulations

Gnomad AFR exome

AF:

0.0288

Gnomad AMR exome

AF:

0.00235

Gnomad ASJ exome

AF:

0.000875

Gnomad EAS exome

AF:

0.000228

Gnomad FIN exome

AF:

0.000287

Gnomad NFE exome

AF:

0.00423

Gnomad OTH exome

AF:

0.00435

GnomAD4 exome

AF:

0.00481

AC:

6965

AN:

1448250

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

3553

AN XY:

720164

show subpopulations

African (AFR)

AF:

0.0288

AC:

939

AN:

32574

American (AMR)

AF:

0.00243

AC:

101

AN:

41642

Ashkenazi Jewish (ASJ)

AF:

0.000554

AC:

AN:

25266

East Asian (EAS)

AF:

0.0000505

AC:

AN:

39590

South Asian (SAS)

AF:

0.00899

AC:

759

AN:

84420

European-Finnish (FIN)

AF:

0.000665

AC:

AN:

52650

Middle Eastern (MID)

AF:

0.00613

AC:

AN:

5714

European-Non Finnish (NFE)

AF:

0.00432

AC:

4782

AN:

1106672

Other (OTH)

AF:

0.00499

AC:

298

AN:

59722

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

372

743

1115

1486

1858

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0108

AC:

1650

AN:

152388

Hom.:

Cov.:

AF XY:

0.0103

AC XY:

771

AN XY:

74526

show subpopulations

African (AFR)

AF:

0.0280

AC:

1166

AN:

41592

American (AMR)

AF:

0.00490

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.000385

AC:

AN:

5192

South Asian (SAS)

AF:

0.00890

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00453

AC:

308

AN:

68040

Other (OTH)

AF:

0.0109

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

172

258

344

430

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00765

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Saldino-Mainzer syndrome

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Saldino-Mainzer syndrome;C4540439:Retinitis pigmentosa 80

Benign:1

Jul 20, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.13

(source)

DANN

Benign

0.54

PhyloP100

-5.4

PromoterAI

-0.013

Neutral

(source)

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over