rs17447091

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The XM_006717819.4(FAS):​c.-1836T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,240 control chromosomes in the GnomAD database, including 1,000 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 ( 1000 hom., cov: 32)

Consequence

FAS
XM_006717819.4 5_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.861
Variant links:
Genes affected
FAS (HGNC:11920): (Fas cell surface death receptor) The protein encoded by this gene is a member of the TNF-receptor superfamily. This receptor contains a death domain. It has been shown to play a central role in the physiological regulation of programmed cell death, and has been implicated in the pathogenesis of various malignancies and diseases of the immune system. The interaction of this receptor with its ligand allows the formation of a death-inducing signaling complex that includes Fas-associated death domain protein (FADD), caspase 8, and caspase 10. The autoproteolytic processing of the caspases in the complex triggers a downstream caspase cascade, and leads to apoptosis. This receptor has been also shown to activate NF-kappaB, MAPK3/ERK1, and MAPK8/JNK, and is found to be involved in transducing the proliferating signals in normal diploid fibroblast and T cells. Several alternatively spliced transcript variants have been described, some of which are candidates for nonsense-mediated mRNA decay (NMD). The isoforms lacking the transmembrane domain may negatively regulate the apoptosis mediated by the full length isoform. [provided by RefSeq, Mar 2011]
ACTA2 (HGNC:130): (actin alpha 2, smooth muscle) This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a smooth muscle actin that is involved in vascular contractility and blood pressure homeostasis. Mutations in this gene cause a variety of vascular diseases, such as thoracic aortic disease, coronary artery disease, stroke, and Moyamoya disease, as well as multisystemic smooth muscle dysfunction syndrome. [provided by RefSeq, Sep 2017]
STAMBPL1 (HGNC:24105): (STAM binding protein like 1) Predicted to enable Lys63-specific deubiquitinase activity and thiol-dependent deubiquitinase. Predicted to be involved in protein K63-linked deubiquitination. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.148 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FASXM_006717819.4 linkuse as main transcriptc.-1836T>A 5_prime_UTR_variant 1/10 XP_006717882.1
ACTA2NM_001141945.3 linkuse as main transcriptc.-24+19427A>T intron_variant NP_001135417.1
ACTA2NM_001320855.2 linkuse as main transcriptc.-24+19510A>T intron_variant NP_001307784.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
STAMBPL1ENST00000371927.7 linkuse as main transcriptc.1255-1670T>A intron_variant 2 ENSP00000360995 Q96FJ0-2
ACTA2ENST00000415557.2 linkuse as main transcriptc.-24+19427A>T intron_variant 3 ENSP00000396730 P1
ACTA2ENST00000458159.6 linkuse as main transcriptc.-24+19510A>T intron_variant 3 ENSP00000398239 P1

Frequencies

GnomAD3 genomes
AF:
0.101
AC:
15363
AN:
152122
Hom.:
999
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0275
Gnomad AMI
AF:
0.0439
Gnomad AMR
AF:
0.0965
Gnomad ASJ
AF:
0.0789
Gnomad EAS
AF:
0.00807
Gnomad SAS
AF:
0.0304
Gnomad FIN
AF:
0.171
Gnomad MID
AF:
0.0696
Gnomad NFE
AF:
0.150
Gnomad OTH
AF:
0.0984
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.101
AC:
15358
AN:
152240
Hom.:
1000
Cov.:
32
AF XY:
0.0991
AC XY:
7374
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0274
Gnomad4 AMR
AF:
0.0962
Gnomad4 ASJ
AF:
0.0789
Gnomad4 EAS
AF:
0.00829
Gnomad4 SAS
AF:
0.0302
Gnomad4 FIN
AF:
0.171
Gnomad4 NFE
AF:
0.150
Gnomad4 OTH
AF:
0.0978
Alfa
AF:
0.115
Hom.:
152
Bravo
AF:
0.0948
Asia WGS
AF:
0.0250
AC:
88
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.45
DANN
Benign
0.64

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: rs17447091; hg19: chr10-90731269; API