chr7-77377400-C-CAAAA

Variant names:

• chr7-77377400-C-CAAAA
• rs56314229
• NM_017439.4:c.577-14_577-11dupTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_017439.4(GSAP):​c.577-14_577-11dupTTTT 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 0.00013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000097 (0 hom.)
• Consequence: GSAP NM_017439.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GSAP	NM_017439.4	c.577-14_577-11dupTTTT		intron_variant	Intron 8 of 30	ENST00000257626.12	NP_059135.2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.000133 AC: 13 AN: 98068 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000121

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000316

Gnomad SAS AF: 0.000339

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000783

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000967 AC: 105 AN: 1086372 Hom.: 0 Cov.: 0 AF XY: 0.000109 AC XY: 58 AN XY: 534516

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000261 AC: 6 AN: 22956

American (AMR) AF: 0.000765 AC: 16 AN: 20904

Ashkenazi Jewish (ASJ) AF: 0.0000670 AC: 1 AN: 14918

East Asian (EAS) AF: 0.00112 AC: 27 AN: 24026

South Asian (SAS) AF: 0.000229 AC: 12 AN: 52468

European-Finnish (FIN) AF: 0.000165 AC: 4 AN: 24172

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3056

European-Non Finnish (NFE) AF: 0.0000386 AC: 34 AN: 881198

Other (OTH) AF: 0.000117 AC: 5 AN: 42674

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000133 AC: 13 AN: 98068 Hom.: 0 Cov.: 0 AF XY: 0.000133 AC XY: 6 AN XY: 45108

African (AFR) AF: 0.000241 AC: 6 AN: 24902

American (AMR) AF: 0.000121 AC: 1 AN: 8258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2670

East Asian (EAS) AF: 0.000316 AC: 1 AN: 3160

South Asian (SAS) AF: 0.000339 AC: 1 AN: 2948

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2950

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 176

European-Non Finnish (NFE) AF: 0.0000783 AC: 4 AN: 51072

Other (OTH) AF: 0.00 AC: 0 AN: 1272

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56314229; hg19: chr7-77006717;