NM_017439.4:c.577-15_577-11delTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_017439.4(GSAP):​c.577-15_577-11delTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0179 in 1,169,796 control chromosomes in the GnomAD database, including 5 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0013 ( 0 hom., cov: 0)
Exomes 𝑓: 0.019 ( 5 hom. )

Consequence

GSAP
NM_017439.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.00
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.0194 (20805/1071720) while in subpopulation AMR AF= 0.0506 (1034/20438). AF 95% confidence interval is 0.048. There are 5 homozygotes in gnomad4_exome. There are 10987 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GSAPNM_017439.4 linkc.577-15_577-11delTTTTT 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.577-15_577-11delTTTTT intron_variant Intron 8 of 30 1 NM_017439.4 ENSP00000257626.7 A4D1B5-1
GSAPENST00000334003.11 linkn.468-15_468-11delTTTTT intron_variant Intron 7 of 18 2

Frequencies

GnomAD3 genomes
AF:
0.00131
AC:
128
AN:
98072
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00293
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000727
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000316
Gnomad SAS
AF:
0.00102
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000861
Gnomad OTH
AF:
0.000786
GnomAD3 exomes
AF:
0.0670
AC:
6387
AN:
95370
Hom.:
3
AF XY:
0.0685
AC XY:
3636
AN XY:
53048
show subpopulations
Gnomad AFR exome
AF:
0.0926
Gnomad AMR exome
AF:
0.0642
Gnomad ASJ exome
AF:
0.0729
Gnomad EAS exome
AF:
0.0482
Gnomad SAS exome
AF:
0.0848
Gnomad FIN exome
AF:
0.0630
Gnomad NFE exome
AF:
0.0634
Gnomad OTH exome
AF:
0.0488
GnomAD4 exome
AF:
0.0194
AC:
20805
AN:
1071720
Hom.:
5
AF XY:
0.0209
AC XY:
10987
AN XY:
526952
show subpopulations
Gnomad4 AFR exome
AF:
0.0384
Gnomad4 AMR exome
AF:
0.0506
Gnomad4 ASJ exome
AF:
0.0286
Gnomad4 EAS exome
AF:
0.0216
Gnomad4 SAS exome
AF:
0.0451
Gnomad4 FIN exome
AF:
0.0274
Gnomad4 NFE exome
AF:
0.0160
Gnomad4 OTH exome
AF:
0.0222
GnomAD4 genome
AF:
0.00133
AC:
130
AN:
98076
Hom.:
0
Cov.:
0
AF XY:
0.00148
AC XY:
67
AN XY:
45128
show subpopulations
Gnomad4 AFR
AF:
0.00301
Gnomad4 AMR
AF:
0.000727
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000317
Gnomad4 SAS
AF:
0.00102
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000862
Gnomad4 OTH
AF:
0.000786

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56314229; hg19: chr7-77006717; API