3-60112188-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002012.4(FHIT):​c.104-98036G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 151,984 control chromosomes in the GnomAD database, including 39,648 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 0.72 ( 39648 hom., cov: 31)

Consequence

FHIT
NM_002012.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.658

Publications

2 publications found
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 was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FHITNM_002012.4 linkc.104-98036G>A intron_variant Intron 5 of 9 ENST00000492590.6 NP_002003.1 P49789A0A024R366

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FHITENST00000492590.6 linkc.104-98036G>A intron_variant Intron 5 of 9 1 NM_002012.4 ENSP00000418582.1 P49789

Frequencies

GnomAD3 genomes
AF:
0.720
AC:
109321
AN:
151866
Hom.:
39616
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.798
Gnomad AMI
AF:
0.599
Gnomad AMR
AF:
0.721
Gnomad ASJ
AF:
0.642
Gnomad EAS
AF:
0.792
Gnomad SAS
AF:
0.810
Gnomad FIN
AF:
0.661
Gnomad MID
AF:
0.611
Gnomad NFE
AF:
0.677
Gnomad OTH
AF:
0.679
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.720
AC:
109410
AN:
151984
Hom.:
39648
Cov.:
31
AF XY:
0.720
AC XY:
53490
AN XY:
74258
show subpopulations
African (AFR)
AF:
0.798
AC:
33076
AN:
41468
American (AMR)
AF:
0.721
AC:
11003
AN:
15268
Ashkenazi Jewish (ASJ)
AF:
0.642
AC:
2215
AN:
3448
East Asian (EAS)
AF:
0.791
AC:
4073
AN:
5146
South Asian (SAS)
AF:
0.811
AC:
3893
AN:
4802
European-Finnish (FIN)
AF:
0.661
AC:
6979
AN:
10560
Middle Eastern (MID)
AF:
0.595
AC:
175
AN:
294
European-Non Finnish (NFE)
AF:
0.677
AC:
46014
AN:
67980
Other (OTH)
AF:
0.682
AC:
1438
AN:
2110
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
1585
3169
4754
6338
7923
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
842
1684
2526
3368
4210
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.708
Hom.:
11269
Bravo
AF:
0.726
Asia WGS
AF:
0.785
AC:
2731
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
1.1
DANN
Benign
0.31
PhyloP100
-0.66
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs9814915; hg19: chr3-60097915; API