4-67571533-C-T

Position:

• chr4-67571533-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The ENST00000265404.7(STAP1):​c.192+378C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.501 in 151,924 control chromosomes in the GnomAD database, including 19,892 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars).

• Frequency: Genomes: 𝑓 0.50 (19892 hom., cov: 32)
• Consequence: STAP1 ENST00000265404.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 4-67571533-C-T is Benign according to our data. Variant chr4-67571533-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAP1	NM_012108.4	c.192+378C>T		intron_variant		ENST00000265404.7	NP_036240.1
STAP1	NM_001317769.2	c.192+378C>T		intron_variant			NP_001304698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAP1	ENST00000265404.7	c.192+378C>T		intron_variant		1	NM_012108.4	ENSP00000265404	P1
STAP1	ENST00000396225.1	c.192+378C>T		intron_variant		1		ENSP00000379527	P1

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76163 AN: 151806 Hom.: 19884 Cov.: 32

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.736

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.557

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.500

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.590

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.501 AC: 76188 AN: 151924 Hom.: 19892 Cov.: 32 AF XY: 0.490 AC XY: 36382 AN XY: 74250

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.557

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.319

Gnomad4 FIN AF: 0.500

Gnomad4 NFE AF: 0.590

Gnomad4 OTH AF: 0.497

Alfa AF: 0.494 Hom.: 5423

Bravo AF: 0.495

Asia WGS AF: 0.241 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.048
DANN	Benign	0.14

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: rs1487383; hg19: chr4-68437251;