rs146128830

Positions:

chr16-1602417-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/20 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

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 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 465318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-1602417-C-T is described in Lovd as [Likely_benign].

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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT140	NM_014714.4 linkuse as main transcript	c.322G>A	p.Val108Met	missense_variant	4/31	ENST00000426508.7	NP_055529.2
LOC105371046	NR_135176.1 linkuse as main transcript	n.60-1998C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT140	ENST00000426508.7 linkuse as main transcript	c.322G>A	p.Val108Met	missense_variant	4/31	5	NM_014714.4	ENSP00000406012	P1	Q96RY7-1
	ENST00000563162.1 linkuse as main transcript	n.60-1998C>T		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes

AF:

0.00694

AC:

1743

AN:

251236

Hom.:

AF XY:

0.00724

AC XY:

983

AN XY:

135850

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 SAS exome

AF:

0.00497

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

Gnomad4 AFR exome

AF:

0.00134

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00494

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00556

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.0107

Gnomad4 OTH exome

AF:

0.00818

GnomAD4 genome

AF:

0.00691

AC:

1052

AN:

152324

Hom.:

Cov.:

AF XY:

0.00718

AC XY:

535

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00490

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00560

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.0111

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00939

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	IFT140: BP4, BS1, BS2 -

Saldino-Mainzer syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Apr 27, 2017	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

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Feb 28, 2017

- -

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

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;.;.

MutationTaster

Benign

0.99

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over