rs3775866

Variant names:

• chr4-67578462-G-A
• rs3775866
• NM_012108.4:c.363+1203G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
STAP1	NM_012108.4	c.363+1203G>A		intron_variant	Intron 4 of 8	ENST00000265404.7	NP_036240.1
STAP1	NM_001317769.2	c.363+1203G>A		intron_variant	Intron 4 of 9		NP_001304698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STAP1	ENST00000265404.7	c.363+1203G>A		intron_variant	Intron 4 of 8	1	NM_012108.4	ENSP00000265404.2
STAP1	ENST00000396225.1	c.363+1203G>A		intron_variant	Intron 4 of 9	1		ENSP00000379527.1

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

African (AFR) AF: 0.195 AC: 8078 AN: 41460

American (AMR) AF: 0.344 AC: 5246 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 910 AN: 3472

East Asian (EAS) AF: 0.250 AC: 1291 AN: 5162

South Asian (SAS) AF: 0.356 AC: 1718 AN: 4820

European-Finnish (FIN) AF: 0.304 AC: 3205 AN: 10554

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18569 AN: 67984

Other (OTH) AF: 0.269 AC: 567 AN: 2110

Alfa AF: 0.273 Hom.: 9697

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
PhyloP100		0.030
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3775866; hg19: chr4-68444180;