4-67577590-T-G

Variant names:

• chr4-67577590-T-G
• rs17088473
• NM_012108.4:c.363+331T>G

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+331T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 151,614 control chromosomes in the GnomAD database, including 5,346 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 (5346 hom., cov: 31)
• Consequence: STAP1 NM_012108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 7 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012108.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAP1	NM_012108.4	MANE Select	c.363+331T>G		intron	N/A	NP_036240.1
	STAP1	NM_001317769.2		c.363+331T>G		intron	N/A	NP_001304698.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAP1	ENST00000265404.7	TSL:1 MANE Select	c.363+331T>G		intron	N/A	ENSP00000265404.2
	STAP1	ENST00000396225.1	TSL:1	c.363+331T>G		intron	N/A	ENSP00000379527.1

Frequencies

GnomAD3 genomes AF: 0.260 AC: 39372 AN: 151496 Hom.: 5348 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.108

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.260 AC: 39381 AN: 151614 Hom.: 5346 Cov.: 31 AF XY: 0.265 AC XY: 19594 AN XY: 74030

African (AFR) AF: 0.195 AC: 8078 AN: 41390

American (AMR) AF: 0.345 AC: 5244 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 893 AN: 3472

East Asian (EAS) AF: 0.244 AC: 1262 AN: 5164

South Asian (SAS) AF: 0.330 AC: 1583 AN: 4794

European-Finnish (FIN) AF: 0.298 AC: 3090 AN: 10378

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

European-Non Finnish (NFE) AF: 0.272 AC: 18485 AN: 67916

Other (OTH) AF: 0.269 AC: 566 AN: 2106

Alfa AF: 0.266 Hom.: 23413

Bravo AF: 0.259

Asia WGS AF: 0.239 AC: 829 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.39
PhyloP100		0.060
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: rs17088473; hg19: chr4-68443308;