rs11924195

chr3-108207671-C-T

Variant summary

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

The NM_018010.4(IFT57):c.586-975G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 152,150 control chromosomes in the GnomAD database, including 701 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 0.091 (701 hom., cov: 31)
• Consequence: IFT57 NM_018010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.339

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=-0.79).
• 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	UniProt
IFT57	NM_018010.4	c.586-975G>A		intron_variant		ENST00000264538.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT57	ENST00000264538.4	c.586-975G>A		intron_variant		1	NM_018010.4	P1
IFT57	ENST00000478157.1	c.*177-975G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 13899 AN: 152032 Hom.: 701 Cov.: 31

Gnomad AFR AF: 0.0777

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0884

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.0722

Gnomad FIN AF: 0.0548

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.102

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

GnomAD4 genome AF: 0.0914 AC: 13909 AN: 152150 Hom.: 701 Cov.: 31 AF XY: 0.0897 AC XY: 6675 AN XY: 74406

Gnomad4 AFR AF: 0.0777

Gnomad4 AMR AF: 0.0883

Gnomad4 ASJ AF: 0.111

Gnomad4 EAS AF: 0.106

Gnomad4 SAS AF: 0.0718

Gnomad4 FIN AF: 0.0548

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.101

Alfa AF: 0.0963 Hom.: 122

Bravo AF: 0.0941

Asia WGS AF: 0.105 AC: 365 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	7.2
Dann	Benign	0.48

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: rs11924195; hg19: chr3-107926518;