Variant 7-77377400-CAAAAAAAAAAAA-CAAAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The ENST00000257626.12(GSAP):c.577-13_577-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.215 in 1,052,978 control chromosomes in the GnomAD database, including 595 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.19 ( 1373 hom., cov: 0)

Exomes 𝑓: 0.22 ( 595 hom. )

Failed GnomAD Quality Control

Consequence

GSAP
ENST00000257626.12 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.00

Variant links:

Genes affected

GSAP (HGNC:28042): (gamma-secretase activating protein) Accumulation of neurotoxic amyloid-beta is a major hallmark of Alzheimer disease (AD; MIM 104300). Formation of amyloid-beta is catalyzed by gamma-secretase (see PSEN1; MIM 104311), a protease with numerous substrates. PION, or GSAP, selectively increases amyloid-beta production through a mechanism involving its interaction with both gamma-secretase and its substrate, the amyloid-beta precursor protein (APP; MIM 104760) C-terminal fragment (APP-CTF) (He et al., 2010 [PubMed 20811458]).[supplied by OMIM, Nov 2010]

GSAP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 7-77377400-CAAA-C is Benign according to our data. Variant chr7-77377400-CAAA-C is described in ClinVar as [Benign]. Clinvar id is 402912.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSAP	NM_017439.4 linkuse as main transcript	c.577-13_577-11del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000257626.12	NP_059135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GSAP	ENST00000257626.12 linkuse as main transcript	c.577-13_577-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017439.4	ENSP00000257626	P1	A4D1B5-1
GSAP	ENST00000334003.11 linkuse as main transcript	n.468-13_468-11del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

18779

AN:

98256

Hom.:

1367

Cov.:

show subpopulations

Gnomad AFR

AF:

0.273

Gnomad AMI

AF:

0.119

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.195

Gnomad EAS

AF:

0.0903

Gnomad SAS

AF:

0.285

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.227

Gnomad NFE

AF:

0.157

Gnomad OTH

AF:

0.194

GnomAD3 exomes

AF:

0.168

AC:

16013

AN:

95370

Hom.:

AF XY:

0.165

AC XY:

8747

AN XY:

53048

show subpopulations

Gnomad AFR exome

AF:

0.174

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.165

Gnomad EAS exome

AF:

0.149

Gnomad SAS exome

AF:

0.171

Gnomad FIN exome

AF:

0.117

Gnomad NFE exome

AF:

0.170

Gnomad OTH exome

AF:

0.181

GnomAD4 exome

AF:

0.215

AC:

226815

AN:

1052978

Hom.:

595

AF XY:

0.214

AC XY:

110682

AN XY:

518066

show subpopulations

Gnomad4 AFR exome

AF:

0.260

Gnomad4 AMR exome

AF:

0.183

Gnomad4 ASJ exome

AF:

0.215

Gnomad4 EAS exome

AF:

0.170

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.160

Gnomad4 NFE exome

AF:

0.217

Gnomad4 OTH exome

AF:

0.221

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.191

AC:

18794

AN:

98260

Hom.:

1373

Cov.:

AF XY:

0.195

AC XY:

8809

AN XY:

45238

show subpopulations

Gnomad4 AFR

AF:

0.273

Gnomad4 AMR

AF:

0.193

Gnomad4 ASJ

AF:

0.195

Gnomad4 EAS

AF:

0.0906

Gnomad4 SAS

AF:

0.284

Gnomad4 FIN

AF:

0.110

Gnomad4 NFE

AF:

0.157

Gnomad4 OTH

AF:

0.196

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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