rs9833533

Variant summary

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

The ENST00000492590.6(FHIT):​c.-17-45541C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0817 in 152,014 control chromosomes in the GnomAD database, including 563 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 0.082 ( 563 hom., cov: 32)

Consequence

FHIT
ENST00000492590.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.370
Variant links:
Genes affected
FHIT (HGNC:3701): (fragile histidine triad diadenosine triphosphatase) The protein encoded by this gene is a P1-P3-bis(5'-adenosyl) triphosphate hydrolase involved in purine metabolism. This gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas. The encoded protein is also a tumor suppressor, as loss of its activity results in replication stress and DNA damage. [provided by RefSeq, Aug 2017]

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=-0.76).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0945 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FHITNM_002012.4 linkuse as main transcriptc.-17-45541C>T intron_variant ENST00000492590.6 NP_002003.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FHITENST00000492590.6 linkuse as main transcriptc.-17-45541C>T intron_variant 1 NM_002012.4 ENSP00000418582 P1

Frequencies

GnomAD3 genomes
AF:
0.0817
AC:
12410
AN:
151896
Hom.:
562
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0969
Gnomad AMI
AF:
0.169
Gnomad AMR
AF:
0.0825
Gnomad ASJ
AF:
0.115
Gnomad EAS
AF:
0.000387
Gnomad SAS
AF:
0.0143
Gnomad FIN
AF:
0.0779
Gnomad MID
AF:
0.177
Gnomad NFE
AF:
0.0793
Gnomad OTH
AF:
0.119
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0817
AC:
12414
AN:
152014
Hom.:
563
Cov.:
32
AF XY:
0.0802
AC XY:
5958
AN XY:
74286
show subpopulations
Gnomad4 AFR
AF:
0.0970
Gnomad4 AMR
AF:
0.0824
Gnomad4 ASJ
AF:
0.115
Gnomad4 EAS
AF:
0.000388
Gnomad4 SAS
AF:
0.0139
Gnomad4 FIN
AF:
0.0779
Gnomad4 NFE
AF:
0.0793
Gnomad4 OTH
AF:
0.118
Alfa
AF:
0.0821
Hom.:
588
Bravo
AF:
0.0826
Asia WGS
AF:
0.0120
AC:
40
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.76
CADD
Benign
15
DANN
Benign
0.75

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

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

Other links and lift over

dbSNP: rs9833533; hg19: chr3-60568253; API