7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAA

Position:

• chr7-77377400-CAAAAAAAAAAAA-CAAAAAAAAAAA

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The NM_017439.4(GSAP):​c.577-11del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.070 (155 hom., cov: 0)
  • Exomes 𝑓: 0.078 (55 hom.)
  • Failed GnomAD Quality Control
• Consequence: GSAP NM_017439.4 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 7-77377400-CA-C is Benign according to our data. Variant chr7-77377400-CA-C is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GSAP	NM_017439.4	c.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	c.577-11del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_017439.4	ENSP00000257626	P1
GSAP	ENST00000334003.11	n.468-11del		splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 6875 AN: 97984 Hom.: 154 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0536

Gnomad AMI AF: 0.0106

Gnomad AMR AF: 0.0485

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.00633

Gnomad SAS AF: 0.0669

Gnomad FIN AF: 0.0861

Gnomad MID AF: 0.0966

Gnomad NFE AF: 0.0819

Gnomad OTH AF: 0.0623

GnomAD4 exome AF: 0.0781 AC: 82741 AN: 1059568 Hom.: 55 Cov.: 0 AF XY: 0.0761 AC XY: 39703 AN XY: 521660

Gnomad4 AFR exome AF: 0.0516

Gnomad4 AMR exome AF: 0.0320

Gnomad4 ASJ exome AF: 0.0886

Gnomad4 EAS exome AF: 0.0486

Gnomad4 SAS exome AF: 0.0486

Gnomad4 FIN exome AF: 0.0724

Gnomad4 NFE exome AF: 0.0826

Gnomad4 OTH exome AF: 0.0759

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0701 AC: 6872 AN: 97988 Hom.: 155 Cov.: 0 AF XY: 0.0690 AC XY: 3110 AN XY: 45084

Gnomad4 AFR AF: 0.0536

Gnomad4 AMR AF: 0.0485

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.00635

Gnomad4 SAS AF: 0.0665

Gnomad4 FIN AF: 0.0861

Gnomad4 NFE AF: 0.0819

Gnomad4 OTH AF: 0.0607

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs56314229; hg19: chr7-77006717;