chr3-129492134-G-C

Position:

chr3-129492134-G-C

Variant summary

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

The NM_052989.3(IFT122):c.1993-7G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,604,430 control chromosomes in the GnomAD database, including 63,735 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 17995 hom., cov: 32)

Exomes 𝑓: 0.20 ( 45740 hom. )

Consequence

IFT122
NM_052989.3 splice_region, intron

Scores

Splicing: ADA: 0.00002742

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.306

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:

IFT122 (HGNC:):

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=-0.82).

BP6

Variant 3-129492134-G-C is Benign according to our data. Variant chr3-129492134-G-C is described in ClinVar as [Benign]. Clinvar id is 194901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-129492134-G-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.82 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.1993-7G>C		splice_region_variant, intron_variant		ENST00000348417.7	NP_443715.1	Q9HBG6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT122	ENST00000348417.7 linkuse as main transcript	c.1993-7G>C		splice_region_variant, intron_variant		1	NM_052989.3	ENSP00000324005.4		Q9HBG6-1

Frequencies

GnomAD3 genomes

AF:

0.382

AC:

58054

AN:

151928

Hom.:

17931

Cov.:

show subpopulations

Gnomad AFR

AF:

0.827

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.345

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.673

Gnomad SAS

AF:

0.380

Gnomad FIN

AF:

0.0745

Gnomad MID

AF:

0.272

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.348

GnomAD3 exomes

AF:

0.282

AC:

70818

AN:

251436

Hom.:

15752

AF XY:

0.272

AC XY:

36985

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.841

Gnomad AMR exome

AF:

0.279

Gnomad ASJ exome

AF:

0.279

Gnomad EAS exome

AF:

0.676

Gnomad SAS exome

AF:

0.373

Gnomad FIN exome

AF:

0.0704

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.203

AC:

295254

AN:

1452384

Hom.:

45740

Cov.:

AF XY:

0.207

AC XY:

149729

AN XY:

723160

show subpopulations

Gnomad4 AFR exome

AF:

0.854

Gnomad4 AMR exome

AF:

0.282

Gnomad4 ASJ exome

AF:

0.281

Gnomad4 EAS exome

AF:

0.661

Gnomad4 SAS exome

AF:

0.372

Gnomad4 FIN exome

AF:

0.0743

Gnomad4 NFE exome

AF:

0.152

Gnomad4 OTH exome

AF:

0.256

GnomAD4 genome

AF:

0.383

AC:

58183

AN:

152046

Hom.:

17995

Cov.:

AF XY:

0.383

AC XY:

28431

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.827

Gnomad4 AMR

AF:

0.345

Gnomad4 ASJ

AF:

0.288

Gnomad4 EAS

AF:

0.672

Gnomad4 SAS

AF:

0.380

Gnomad4 FIN

AF:

0.0745

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.349

Alfa

AF:

0.161

Hom.:

827

Bravo

AF:

0.420

EpiCase

AF:

0.173

EpiControl

AF:

0.179

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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	PreventionGenetics, part of Exact Sciences	-	- -
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. -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jun 09, 2015	- -

Cranioectodermal dysplasia 1

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

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

-0.82

CADD

Benign

1.7

DANN

Benign

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.010

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