4-67568137-C-T

Variant names:

• chr4-67568137-C-T
• rs6826751
• NM_012108.4:c.121-2947C>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.121-2947C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,990 control chromosomes in the GnomAD database, including 22,656 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 0.53 (22656 hom., cov: 32)
• Consequence: STAP1 NM_012108.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00300
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.629 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAP1	NM_012108.4	MANE Select	c.121-2947C>T		intron	N/A	NP_036240.1
	STAP1	NM_001317769.2		c.121-2947C>T		intron	N/A	NP_001304698.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAP1	ENST00000265404.7	TSL:1 MANE Select	c.121-2947C>T		intron	N/A	ENSP00000265404.2
	STAP1	ENST00000396225.1	TSL:1	c.121-2947C>T		intron	N/A	ENSP00000379527.1
	STAP1	ENST00000894638.1		c.121-2947C>T		intron	N/A	ENSP00000564697.1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80897 AN: 151872 Hom.: 22643 Cov.: 32

Gnomad AFR AF: 0.440

Gnomad AMI AF: 0.788

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.626

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.354

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.542

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.533 AC: 80936 AN: 151990 Hom.: 22656 Cov.: 32 AF XY: 0.525 AC XY: 38979 AN XY: 74288

African (AFR) AF: 0.440 AC: 18232 AN: 41420

American (AMR) AF: 0.428 AC: 6535 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.626 AC: 2171 AN: 3470

East Asian (EAS) AF: 0.186 AC: 962 AN: 5180

South Asian (SAS) AF: 0.353 AC: 1705 AN: 4826

European-Finnish (FIN) AF: 0.594 AC: 6245 AN: 10516

Middle Eastern (MID) AF: 0.545 AC: 158 AN: 290

European-Non Finnish (NFE) AF: 0.634 AC: 43131 AN: 67982

Other (OTH) AF: 0.511 AC: 1080 AN: 2114

Alfa AF: 0.555 Hom.: 9258

Bravo AF: 0.517

Asia WGS AF: 0.272 AC: 946 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	2.8
DANN	Benign	0.51
PhyloP100		-0.0030
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: rs6826751; hg19: chr4-68433855; COSMIC: COSV107204775;