rs3138373

Positions:

• chr3-129430178-T-C
• chr3-129430178-T-G

Variant summary

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

The ENST00000687461.1(IFT122):​n.145+360T>C variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,196 control chromosomes in the GnomAD database, including 1,673 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 0.13 (1673 hom., cov: 33)
• Consequence: IFT122 ENST00000687461.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

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=-0.9).
• 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	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT122	ENST00000687461.1	n.145+360T>C		intron_variant, non_coding_transcript_variant
IFT122	ENST00000693654.1	n.212+360T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20002 AN: 152078 Hom.: 1668 Cov.: 33

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.0812

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0397

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0944

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.132 AC: 20031 AN: 152196 Hom.: 1673 Cov.: 33 AF XY: 0.131 AC XY: 9765 AN XY: 74426

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.106

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.0806

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.0397

Gnomad4 NFE AF: 0.0944

Gnomad4 OTH AF: 0.144

Alfa AF: 0.101 Hom.: 901

Bravo AF: 0.138

Asia WGS AF: 0.204 AC: 714 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.2
DANN	Benign	0.68

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3138373; hg19: chr3-129149021;