7-77407258-A-G

Position:

• chr7-77407258-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
GSAP	NM_017439.4	c.110-1153T>C		intron_variant		ENST00000257626.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GSAP	ENST00000257626.12	c.110-1153T>C		intron_variant		1	NM_017439.4	P1
GSAP	ENST00000430584.1	n.362-1153T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0793

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.0605

Gnomad4 SAS AF: 0.229

Gnomad4 FIN AF: 0.0645

Gnomad4 NFE AF: 0.0772

Gnomad4 OTH AF: 0.104

Alfa AF: 0.0890 Hom.: 174

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

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: rs7793977; hg19: chr7-77036575;