rs146128830

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_014714.4(IFT140):c.322G>A(p.Val108Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00927 in 1,614,188 control chromosomes in the GnomAD database, including 85 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0069 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0095 ( 80 hom. )

Consequence

IFT140
NM_014714.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.0220

Publications

11 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:

ENSG00000260989 (HGNC:):

ENSG00000260989 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=0.015878737).

BP6

Variant 16-1602417-C-T is Benign according to our data. Variant chr16-1602417-C-T is described in ClinVar as Benign. ClinVar VariationId is 465318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00691 (1052/152324) while in subpopulation NFE AF = 0.0111 (754/68034). AF 95% confidence interval is 0.0104. There are 5 homozygotes in GnomAd4. There are 535 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IFT140	NM_014714.4 link	c.322G>A	p.Val108Met	missense_variant	Exon 4 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.322G>A	p.Val108Met	missense_variant	Exon 4 of 31	5	NM_014714.4	ENSP00000406012.2		Q96RY7-1

Frequencies

GnomAD3 genomes

AF:

0.00692

AC:

1054

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00183

Gnomad AMI

AF:

0.00330

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00580

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00694

AC:

1743

AN:

251236

AF XY:

0.00724

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00516

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.0146

Gnomad NFE exome

AF:

0.00964

Gnomad OTH exome

AF:

0.00668

GnomAD4 exome

AF:

0.00952

AC:

13916

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00946

AC XY:

6883

AN XY:

727232

show subpopulations

African (AFR)

AF:

0.00134

AC:

AN:

33480

American (AMR)

AF:

0.00170

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00494

AC:

129

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39696

South Asian (SAS)

AF:

0.00556

AC:

480

AN:

86256

European-Finnish (FIN)

AF:

0.0136

AC:

726

AN:

53420

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0107

AC:

11942

AN:

1111994

Other (OTH)

AF:

0.00818

AC:

494

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

808

1617

2425

3234

4042

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

454

908

1362

1816

2270

<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:

0.00691

AC:

1052

AN:

152324

Hom.:

Cov.:

AF XY:

0.00718

AC XY:

535

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00180

AC:

AN:

41588

American (AMR)

AF:

0.00229

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.00560

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.0123

AC:

130

AN:

10612

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0111

AC:

754

AN:

68034

Other (OTH)

AF:

0.00284

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

115

173

230

288

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:

0.00896

Hom.:

Bravo

AF:

0.00566

TwinsUK

AF:

0.00863

AC:

ALSPAC

AF:

0.0106

AC:

ESP6500AA

AF:

0.00273

AC:

ESP6500EA

AF:

0.00942

AC:

ExAC

AF:

0.00690

AC:

838

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00867

EpiControl

AF:

0.00907

ClinVar

Significance: Benign

Submissions summary: Benign:5

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

- -

May 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

IFT140: BP4, BS1, BS2 -

Saldino-Mainzer syndrome

Benign:2

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

not specified

Benign:1

Feb 28, 2017

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.021

T;T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.66

FATHMM_MKL

Benign

0.045

LIST_S2

Uncertain

0.86

D;T;T

MetaRNN

Benign

0.016

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.5

M;.;.

PhyloP100

0.022

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.71

N;N;N

REVEL

Benign

0.24

Sift

Uncertain

0.022

D;D;D

Sift4G

Uncertain

0.044

D;.;.

Polyphen

0.98

D;.;.

Vest4

0.54

MVP

0.59

MPC

0.34

ClinPred

0.019

GERP RS

-1.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.031

gMVP

0.23

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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