3-129467081-G-A

Position:

chr3-129467081-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052989.3(IFT122):c.740+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 1,610,426 control chromosomes in the GnomAD database, including 12,066 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1709 hom., cov: 33)

Exomes 𝑓: 0.11 ( 10357 hom. )

Consequence

IFT122
NM_052989.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.274

Variant links:

Genes affected

IFT122 (HGNC:13556): (intraflagellar transport 122) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. This cytoplasmic protein contains seven WD repeats and an AF-2 domain which function by recruiting coregulatory molecules and in transcriptional activation. Mutations in this gene cause cranioectodermal dysplasia-1. A related pseudogene is located on chromosome 3. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2013]

IFT122 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 (BayesDel_noAF=-0.92).

BP6

Variant 3-129467081-G-A is Benign according to our data. Variant chr3-129467081-G-A is described in ClinVar as [Benign]. Clinvar id is 262273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129467081-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT122	NM_052989.3 linkuse as main transcript	c.740+15G>A		intron_variant		ENST00000348417.7	NP_443715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000348417.7 linkuse as main transcript	c.740+15G>A		intron_variant		1	NM_052989.3	ENSP00000324005		Q9HBG6-1

Frequencies

GnomAD3 genomes

AF:

0.132

AC:

20157

AN:

152144

Hom.:

1703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.220

Gnomad AMI

AF:

0.105

Gnomad AMR

AF:

0.106

Gnomad ASJ

AF:

0.166

Gnomad EAS

AF:

0.0817

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.0390

Gnomad MID

AF:

0.101

Gnomad NFE

AF:

0.0942

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.117

AC:

29110

AN:

249336

Hom.:

2326

AF XY:

0.124

AC XY:

16657

AN XY:

134858

show subpopulations

Gnomad AFR exome

AF:

0.223

Gnomad AMR exome

AF:

0.0708

Gnomad ASJ exome

AF:

0.167

Gnomad EAS exome

AF:

0.0769

Gnomad SAS exome

AF:

0.250

Gnomad FIN exome

AF:

0.0387

Gnomad NFE exome

AF:

0.0955

Gnomad OTH exome

AF:

0.122

GnomAD4 exome

AF:

0.108

AC:

157776

AN:

1458164

Hom.:

10357

Cov.:

AF XY:

0.113

AC XY:

81840

AN XY:

725496

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.0739

Gnomad4 ASJ exome

AF:

0.168

Gnomad4 EAS exome

AF:

0.0644

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.0409

Gnomad4 NFE exome

AF:

0.0974

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.133

AC:

20183

AN:

152262

Hom.:

1709

Cov.:

AF XY:

0.132

AC XY:

9835

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.220

Gnomad4 AMR

AF:

0.106

Gnomad4 ASJ

AF:

0.166

Gnomad4 EAS

AF:

0.0811

Gnomad4 SAS

AF:

0.240

Gnomad4 FIN

AF:

0.0390

Gnomad4 NFE

AF:

0.0942

Gnomad4 OTH

AF:

0.144

Alfa

AF:

0.120

Hom.:

273

Bravo

AF:

0.139

Asia WGS

AF:

0.204

AC:

714

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 13, 2017	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Cranioectodermal dysplasia 1

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Cranioectodermal dysplasia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

3.2

DANN

Benign

0.61

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

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