16-1564146-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014714.4(IFT140):c.1918G>A(p.Asp640Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0042 in 1,579,900 control chromosomes in the GnomAD database, including 240 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 115 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 125 hom. )

Consequence

IFT140
NM_014714.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.360

Publications

2 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: G2P, Labcorp Genetics (formerly Invitae), 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031694174).

BP6

Variant 16-1564146-C-T is Benign according to our data. Variant chr16-1564146-C-T is described in ClinVar as Benign. ClinVar VariationId is 318183.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014714.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IFT140	NM_014714.4	MANE Select	c.1918G>A	p.Asp640Asn	missense	Exon 17 of 31	NP_055529.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
IFT140	ENST00000426508.7	TSL:5 MANE Select	c.1918G>A	p.Asp640Asn	missense	Exon 17 of 31	ENSP00000406012.2	Q96RY7-1
IFT140	ENST00000889170.1		c.1918G>A	p.Asp640Asn	missense	Exon 16 of 30	ENSP00000559229.1
IFT140	ENST00000962400.1		c.1918G>A	p.Asp640Asn	missense	Exon 16 of 30	ENSP00000632459.1

Frequencies

GnomAD3 genomes

AF:

0.0217

AC:

3296

AN:

152160

Hom.:

116

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0745

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00929

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.0158

GnomAD2 exomes

AF:

0.00568

AC:

1377

AN:

242570

AF XY:

0.00406

show subpopulations

Gnomad AFR exome

AF:

0.0744

Gnomad AMR exome

AF:

0.00416

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000327

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.00443

GnomAD4 exome

AF:

0.00234

AC:

3340

AN:

1427622

Hom.:

125

Cov.:

AF XY:

0.00198

AC XY:

1397

AN XY:

705224

show subpopulations

African (AFR)

AF:

0.0770

AC:

2493

AN:

32378

American (AMR)

AF:

0.00477

AC:

205

AN:

43004

Ashkenazi Jewish (ASJ)

AF:

0.0000394

AC:

AN:

25390

East Asian (EAS)

AF:

0.00

AC:

AN:

38310

South Asian (SAS)

AF:

0.0000715

AC:

AN:

83874

European-Finnish (FIN)

AF:

0.000359

AC:

AN:

52930

Middle Eastern (MID)

AF:

0.00338

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.000273

AC:

297

AN:

1087496

Other (OTH)

AF:

0.00512

AC:

300

AN:

58626

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.444

Heterozygous variant carriers

148

296

445

593

741

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<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:

0.0216

AC:

3294

AN:

152278

Hom.:

115

Cov.:

AF XY:

0.0209

AC XY:

1558

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.0742

AC:

3084

AN:

41548

American (AMR)

AF:

0.00928

AC:

142

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.000415

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000456

AC:

AN:

68032

Other (OTH)

AF:

0.0156

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

154

309

463

618

772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

160

<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:

0.00829

Hom.:

Bravo

AF:

0.0252

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0734

AC:

323

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00691

AC:

839

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Saldino-Mainzer syndrome (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.6

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.012

Eigen

Benign

-0.82

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.55

MetaRNN

Benign

0.0032

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

PhyloP100

0.36

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.71

REVEL

Benign

0.071

Sift

Benign

0.19

Sift4G

Benign

0.45

Polyphen

0.0

Vest4

0.11

MVP

0.59

MPC

0.067

ClinPred

0.00085

GERP RS

2.0

Varity_R

0.032

gMVP

0.24

Mutation Taster

=96/4

polymorphism (auto)

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over