Variant NM_017439.4:c.577-12_577-11dupTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_017439.4(GSAP):c.577-12_577-11dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.013 ( 27 hom., cov: 0)

Exomes 𝑓: 0.0044 ( 2 hom. )

Consequence

GSAP
NM_017439.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0132 (1295/98022) while in subpopulation AMR AF= 0.0383 (316/8246). AF 95% confidence interval is 0.0348. There are 27 homozygotes in gnomad4. There are 629 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 27 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSAP	NM_017439.4 link	c.577-12_577-11dupTT		intron_variant	Intron 8 of 30	ENST00000257626.12	NP_059135.2	A4D1B5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSAP	ENST00000257626.12 link	c.577-11_577-10insTT		intron_variant	Intron 8 of 30	1	NM_017439.4	ENSP00000257626.7		A4D1B5-1
GSAP	ENST00000334003.11 link	n.468-11_468-10insTT		intron_variant	Intron 7 of 18	2

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

1297

AN:

98020

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0238

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0386

Gnomad ASJ

AF:

0.00412

Gnomad EAS

AF:

0.0245

Gnomad SAS

AF:

0.00780

Gnomad FIN

AF:

0.000339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00509

Gnomad OTH

AF:

0.0118

GnomAD4 exome

AF:

0.00437

AC:

4731

AN:

1082486

Hom.:

Cov.:

AF XY:

0.00429

AC XY:

2284

AN XY:

532692

show subpopulations

Gnomad4 AFR exome

AF:

0.0139

Gnomad4 AMR exome

AF:

0.0137

Gnomad4 ASJ exome

AF:

0.00329

Gnomad4 EAS exome

AF:

0.0236

Gnomad4 SAS exome

AF:

0.00560

Gnomad4 FIN exome

AF:

0.00352

Gnomad4 NFE exome

AF:

0.00331

Gnomad4 OTH exome

AF:

0.00525

GnomAD4 genome

AF:

0.0132

AC:

1295

AN:

98022

Hom.:

Cov.:

AF XY:

0.0139

AC XY:

629

AN XY:

45102

show subpopulations

Gnomad4 AFR

AF:

0.0238

Gnomad4 AMR

AF:

0.0383

Gnomad4 ASJ

AF:

0.00412

Gnomad4 EAS

AF:

0.0246

Gnomad4 SAS

AF:

0.00750

Gnomad4 FIN

AF:

0.000339

Gnomad4 NFE

AF:

0.00509

Gnomad4 OTH

AF:

0.0118

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over