rs10511268

Positions:

• chr3-108183236-C-T

Variant summary

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

The ENST00000264538.4(IFT57):​c.777+8285G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0963 in 151,986 control chromosomes in the GnomAD database, including 761 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 0.096 (761 hom., cov: 32)
• Consequence: IFT57 ENST00000264538.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

IFT57 (HGNC:17367): (intraflagellar transport 57) Predicted to enable DNA binding activity. Acts upstream of or within activation of cysteine-type endopeptidase activity involved in apoptotic process; apoptotic process; and regulation of apoptotic process. Predicted to be located in ciliary basal body. Predicted to be part of axoneme and intraciliary transport particle B. Predicted to be active in Golgi apparatus; centrosome; and cilium. Implicated in orofaciodigital syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IFT57	NM_018010.4	c.777+8285G>A		intron_variant		ENST00000264538.4	NP_060480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IFT57	ENST00000264538.4	c.777+8285G>A		intron_variant		1	NM_018010.4	ENSP00000264538	P1
IFT57	ENST00000478157.1	c.*368+8285G>A		intron_variant, NMD_transcript_variant		5		ENSP00000417768

Frequencies

GnomAD3 genomes AF: 0.0964 AC: 14633 AN: 151868 Hom.: 761 Cov.: 32

Gnomad AFR AF: 0.0941

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.0906

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0552

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.0963 AC: 14643 AN: 151986 Hom.: 761 Cov.: 32 AF XY: 0.0947 AC XY: 7029 AN XY: 74260

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.0905

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.0732

Gnomad4 FIN AF: 0.0552

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.104

Alfa AF: 0.101 Hom.: 231

Bravo AF: 0.0996

Asia WGS AF: 0.108 AC: 376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.0
DANN	Benign	0.54

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: rs10511268; hg19: chr3-107902083;