rs2311394

Positions:

• chr3-129440996-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_052989.3(IFT122):​c.41+625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 152,166 control chromosomes in the GnomAD database, including 2,859 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (2859 hom., cov: 32)
• Consequence: IFT122 NM_052989.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.344

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT122	NM_052989.3	c.41+625A>G		intron_variant		ENST00000348417.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT122	ENST00000348417.7	c.41+625A>G		intron_variant		1	NM_052989.3

Frequencies

GnomAD3 genomes AF: 0.162 AC: 24569 AN: 152048 Hom.: 2850 Cov.: 32

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.169

Gnomad EAS AF: 0.0820

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0950

Gnomad OTH AF: 0.166

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.162 AC: 24608 AN: 152166 Hom.: 2859 Cov.: 32 AF XY: 0.161 AC XY: 11968 AN XY: 74418

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.122

Gnomad4 ASJ AF: 0.169

Gnomad4 EAS AF: 0.0814

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0951

Gnomad4 OTH AF: 0.168

Alfa AF: 0.135 Hom.: 560

Bravo AF: 0.173

Asia WGS AF: 0.215 AC: 750 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.51

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

Other links and lift over

dbSNP: rs2311394; hg19: chr3-129159839;