GeneBe

chr7-77377400-CAAAAAAAAAA-C

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_017439.4(GSAP):​c.577-20_577-11delTTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000267 in 1,086,430 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 0)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

GSAP
NM_017439.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.21

Publications

0 publications found
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]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GSAPNM_017439.4 linkc.577-20_577-11delTTTTTTTTTT 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
GSAPENST00000257626.12 linkc.577-20_577-11delTTTTTTTTTT intron_variant Intron 8 of 30 1 NM_017439.4 ENSP00000257626.7 A4D1B5-1
GSAPENST00000334003.11 linkn.468-20_468-11delTTTTTTTTTT intron_variant Intron 7 of 18 2

Frequencies

GnomAD3 genomes
Cov.:
0
GnomAD4 exome
AF:
0.0000267
AC:
29
AN:
1086430
Hom.:
0
AF XY:
0.0000318
AC XY:
17
AN XY:
534552
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
22962
American (AMR)
AF:
0.00
AC:
0
AN:
20908
Ashkenazi Jewish (ASJ)
AF:
0.0000670
AC:
1
AN:
14918
East Asian (EAS)
AF:
0.00
AC:
0
AN:
24036
South Asian (SAS)
AF:
0.000114
AC:
6
AN:
52462
European-Finnish (FIN)
AF:
0.0000827
AC:
2
AN:
24172
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
3056
European-Non Finnish (NFE)
AF:
0.0000216
AC:
19
AN:
881238
Other (OTH)
AF:
0.0000234
AC:
1
AN:
42678
⚠️ 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.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.256
Heterozygous variant carriers
0
4
8
11
15
19
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.2

Splicing

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

Publications

Other links and lift over

dbSNP: rs56314229; hg19: chr7-77006717; API