Variant 4-67570978-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000265404.7(STAP1):c.121-106C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0127 in 887,174 control chromosomes in the GnomAD database, including 104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0099 ( 9 hom., cov: 32)

Exomes 𝑓: 0.013 ( 95 hom. )

Consequence

STAP1
ENST00000265404.7 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0480

Variant links:

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]

STAP1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 4-67570978-C-T is Benign according to our data. Variant chr4-67570978-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1194139.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0132 (9729/735006) while in subpopulation NFE AF= 0.0164 (7865/479986). AF 95% confidence interval is 0.0161. There are 95 homozygotes in gnomad4_exome. There are 5166 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STAP1	NM_012108.4 linkuse as main transcript	c.121-106C>T		intron_variant		ENST00000265404.7	NP_036240.1
STAP1	NM_001317769.2 linkuse as main transcript	c.121-106C>T		intron_variant			NP_001304698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STAP1	ENST00000265404.7 linkuse as main transcript	c.121-106C>T		intron_variant		1	NM_012108.4	ENSP00000265404	P1
STAP1	ENST00000396225.1 linkuse as main transcript	c.121-106C>T		intron_variant		1		ENSP00000379527	P1

Frequencies

GnomAD3 genomes

AF:

0.00988

AC:

1502

AN:

152050

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00227

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.00728

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00311

Gnomad FIN

AF:

0.0163

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0154

Gnomad OTH

AF:

0.0125

GnomAD4 exome

AF:

0.0132

AC:

9729

AN:

735006

Hom.:

AF XY:

0.0132

AC XY:

5166

AN XY:

391876

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00573

Gnomad4 ASJ exome

AF:

0.00504

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00415

Gnomad4 FIN exome

AF:

0.0176

Gnomad4 NFE exome

AF:

0.0164

Gnomad4 OTH exome

AF:

0.0105

GnomAD4 genome

AF:

0.00986

AC:

1501

AN:

152168

Hom.:

Cov.:

AF XY:

0.00956

AC XY:

711

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00226

Gnomad4 AMR

AF:

0.00727

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.000385

Gnomad4 SAS

AF:

0.00290

Gnomad4 FIN

AF:

0.0163

Gnomad4 NFE

AF:

0.0154

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.0143

Hom.:

Bravo

AF:

0.00892

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 29, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

DANN

Benign

0.19

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over