rs1289745

Positions:

• chr3-108207411-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.586-715G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 152,068 control chromosomes in the GnomAD database, including 47,268 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 0.78 (47268 hom., cov: 31)
• Consequence: IFT57 NM_018010.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IFT57	NM_018010.4	c.586-715G>A		intron_variant		ENST00000264538.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IFT57	ENST00000264538.4	c.586-715G>A		intron_variant		1	NM_018010.4	P1
IFT57	ENST00000478157.1	c.*177-715G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.780 AC: 118563 AN: 151950 Hom.: 47250 Cov.: 31

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.794

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.853

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.738

Gnomad FIN AF: 0.870

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.785

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

GnomAD4 genome AF: 0.780 AC: 118625 AN: 152068 Hom.: 47268 Cov.: 31 AF XY: 0.775 AC XY: 57609 AN XY: 74356

Gnomad4 AFR AF: 0.689

Gnomad4 AMR AF: 0.721

Gnomad4 ASJ AF: 0.853

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.739

Gnomad4 FIN AF: 0.870

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.783

Alfa AF: 0.798 Hom.: 9184

Bravo AF: 0.764

Asia WGS AF: 0.532 AC: 1854 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.2
DANN	Benign	0.39

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: rs1289745; hg19: chr3-107926258;