rs3775866

Positions:

• chr4-67578462-G-A
• chr4-67578462-G-T

Variant summary

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

The NM_012108.4(STAP1):​c.363+1203G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.262 in 152,034 control chromosomes in the GnomAD database, including 5,437 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 0.26 (5437 hom., cov: 31)
• Consequence: STAP1 NM_012108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0300

Genes affected

STAP1 (HGNC:24133): (signal transducing adaptor family member 1) The protein encoded by this gene contains a proline-rich region, a pleckstrin homology (PH) domain, and a region in the carboxy terminal half with similarity to the Src Homology 2 (SH2) domain. This protein is a substrate of tyrosine-protein kinase Tec, and its interaction with tyrosine-protein kinase Tec is phosphorylation-dependent. This protein is thought to participate in a positive feedback loop by upregulating the activity of tyrosine-protein kinase Tec. Variants of this gene have been associated with autosomal-dominant hypercholesterolemia (ADH), which is characterized by elevated low-density lipoprotein cholesterol levels and in increased risk of coronary vascular disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAP1	NM_012108.4	c.363+1203G>A		intron_variant		ENST00000265404.7	NP_036240.1
STAP1	NM_001317769.2	c.363+1203G>A		intron_variant			NP_001304698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAP1	ENST00000265404.7	c.363+1203G>A		intron_variant		1	NM_012108.4	ENSP00000265404	P1
STAP1	ENST00000396225.1	c.363+1203G>A		intron_variant		1		ENSP00000379527	P1

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39756 AN: 151916 Hom.: 5438 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.110

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.356

Gnomad FIN AF: 0.304

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.262 AC: 39766 AN: 152034 Hom.: 5437 Cov.: 31 AF XY: 0.267 AC XY: 19854 AN XY: 74286

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.344

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.356

Gnomad4 FIN AF: 0.304

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.269

Alfa AF: 0.275 Hom.: 7727

Bravo AF: 0.259

Asia WGS AF: 0.249 AC: 866 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.36

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: rs3775866; hg19: chr4-68444180;