4-67581531-A-G

Position:

• chr4-67581531-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_012108.4(STAP1):​c.530+60A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,537,914 control chromosomes in the GnomAD database, including 38,752 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3171 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35581 hom.)
• Consequence: STAP1 NM_012108.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.308

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP6: Variant 4-67581531-A-G is Benign according to our data. Variant chr4-67581531-A-G is described in ClinVar as [Benign]. Clinvar id is 1262529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.29 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STAP1	NM_012108.4	c.530+60A>G		intron_variant		ENST00000265404.7
STAP1	NM_001317769.2	c.530+60A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STAP1	ENST00000265404.7	c.530+60A>G		intron_variant		1	NM_012108.4	P1
STAP1	ENST00000396225.1	c.530+60A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30072 AN: 152056 Hom.: 3176 Cov.: 33

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.223 AC: 309202 AN: 1385740 Hom.: 35581 AF XY: 0.226 AC XY: 154373 AN XY: 683322

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.149

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.312

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.221

Gnomad4 OTH exome AF: 0.222

GnomAD4 genome AF: 0.198 AC: 30060 AN: 152174 Hom.: 3171 Cov.: 33 AF XY: 0.202 AC XY: 15049 AN XY: 74396

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.228

Gnomad4 EAS AF: 0.229

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.222

Gnomad4 OTH AF: 0.190

Alfa AF: 0.215 Hom.: 6869

Bravo AF: 0.183

Asia WGS AF: 0.213 AC: 740 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	11
DANN	Benign	0.57

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: rs2242330; hg19: chr4-68447249; COSMIC: COSV55327755;