rs79494390

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.3743T>C(p.Ile1248Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00354 in 1,614,174 control chromosomes in the GnomAD database, including 115 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 59 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 56 hom. )

Consequence

IFT140
NM_014714.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 9.24

Publications

4 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008605152).

BP6

Variant 16-1520261-A-G is Benign according to our data. Variant chr16-1520261-A-G is described in ClinVar as Benign. ClinVar VariationId is 317998.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0509 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT140	NM_014714.4 link	c.3743T>C	p.Ile1248Thr	missense_variant	Exon 28 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.3743T>C	p.Ile1248Thr	missense_variant	Exon 28 of 31	5	NM_014714.4	ENSP00000406012.2		Q96RY7-1

Frequencies

GnomAD3 genomes

AF:

0.0159

AC:

2423

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00837

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000579

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.0153

GnomAD2 exomes

AF:

0.00483

AC:

1215

AN:

251490

AF XY:

0.00383

show subpopulations

Gnomad AFR exome

AF:

0.0543

Gnomad AMR exome

AF:

0.00309

Gnomad ASJ exome

AF:

0.00496

Gnomad EAS exome

AF:

0.000217

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000624

Gnomad OTH exome

AF:

0.00358

GnomAD4 exome

AF:

0.00224

AC:

3272

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1523

AN XY:

727242

show subpopulations

African (AFR)

AF:

0.0553

AC:

1850

AN:

33480

American (AMR)

AF:

0.00420

AC:

188

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00551

AC:

144

AN:

26136

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00283

AC:

244

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.0132

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000402

AC:

447

AN:

1112010

Other (OTH)

AF:

0.00532

AC:

321

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

214

428

642

856

1070

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<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:

0.0160

AC:

2442

AN:

152288

Hom.:

Cov.:

AF XY:

0.0155

AC XY:

1153

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0527

AC:

2190

AN:

41560

American (AMR)

AF:

0.00836

AC:

128

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.000580

AC:

AN:

5170

South Asian (SAS)

AF:

0.00393

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000632

AC:

AN:

68010

Other (OTH)

AF:

0.0151

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

117

233

350

466

583

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00773

Hom.:

Bravo

AF:

0.0185

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0491

AC:

216

ESP6500EA

AF:

0.000581

AC:

ExAC

AF:

0.00567

AC:

688

Asia WGS

AF:

0.00953

AC:

AN:

3478

EpiCase

AF:

0.000491

EpiControl

AF:

0.000771

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 09, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

.;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;D

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M

PhyloP100

9.2

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-4.1

D;D

REVEL

Uncertain

0.34

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0040

D;D

Polyphen

0.97

.;D

Vest4

0.84

MVP

0.74

MPC

0.32

ClinPred

0.033

GERP RS

6.0

PromoterAI

-0.074

Neutral

(source)

Varity_R

0.39

gMVP

0.52

Mutation Taster

=48/52

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over