rs7793977

Variant names:

• chr7-77407258-A-G
• rs7793977
• NM_017439.4:c.110-1153T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017439.4(GSAP):​c.110-1153T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,214 control chromosomes in the GnomAD database, including 900 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.10 (900 hom., cov: 32)
• Consequence: GSAP NM_017439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.262
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSAP	NM_017439.4	c.110-1153T>C		intron_variant	Intron 1 of 30	ENST00000257626.12	NP_059135.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GSAP	ENST00000257626.12	c.110-1153T>C		intron_variant	Intron 1 of 30	1	NM_017439.4	ENSP00000257626.7
GSAP	ENST00000430584.1	n.362-1153T>C		intron_variant	Intron 1 of 4	5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15365 AN: 152096 Hom.: 889 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.0308

Gnomad AMR AF: 0.0795

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.0606

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.0645

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.0937

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

GnomAD4 genome AF: 0.101 AC: 15401 AN: 152214 Hom.: 900 Cov.: 32 AF XY: 0.104 AC XY: 7744 AN XY: 74422

African (AFR) AF: 0.150 AC: 6217 AN: 41518

American (AMR) AF: 0.0793 AC: 1212 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 350 AN: 3468

East Asian (EAS) AF: 0.0605 AC: 314 AN: 5190

South Asian (SAS) AF: 0.229 AC: 1104 AN: 4828

European-Finnish (FIN) AF: 0.0645 AC: 683 AN: 10596

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5250 AN: 68006

Other (OTH) AF: 0.104 AC: 220 AN: 2114

Alfa AF: 0.0891 Hom.: 226

Bravo AF: 0.100

Asia WGS AF: 0.193 AC: 668 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.86
DANN	Benign	0.74
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7793977; hg19: chr7-77036575;