3-60210809-G-T
Position:
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1
The NM_002012.4(FHIT):c.104-196657C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 151,966 control chromosomes in the GnomAD database, including 1,043 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).
Frequency
Genomes: 𝑓 0.12 ( 1043 hom., cov: 31)
Consequence
FHIT
NM_002012.4 intron
NM_002012.4 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.06
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 = 0.133 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
FHIT | NM_002012.4 | c.104-196657C>A | intron_variant | ENST00000492590.6 | NP_002003.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
FHIT | ENST00000492590.6 | c.104-196657C>A | intron_variant | 1 | NM_002012.4 | ENSP00000418582.1 | ||||
FHIT | ENST00000476844.5 | c.104-196657C>A | intron_variant | 1 | ENSP00000417557.1 | |||||
FHIT | ENST00000468189.5 | c.104-196657C>A | intron_variant | 2 | ENSP00000417480.1 | |||||
FHIT | ENST00000488467.5 | c.104-196657C>A | intron_variant | 3 | ENSP00000418596.1 |
Frequencies
GnomAD3 genomes AF: 0.115 AC: 17486AN: 151848Hom.: 1042 Cov.: 31
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We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome AF: 0.115 AC: 17492AN: 151966Hom.: 1043 Cov.: 31 AF XY: 0.118 AC XY: 8722AN XY: 74224
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474
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3476
ClinVar
Significance: association
Submissions summary: Other:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Lip and oral cavity carcinoma Other:1
association, criteria provided, single submitter | case-control | Department of Biological Science, Sunandan Divatia School of Science, NMIMS University | Jan 01, 2016 | A significant association of rs11130760 (FHIT) GG (odds ratio [OR] 1.41; 95% confidence interval [CI] 1.08-1.84) indicated increased risk. The SNP rs11130760 (FHIT) wild-type (WT) allele G indicated an increased risk for oral cancer (OR 1.38; 95% CI 1.09-1.73), whereas SNP allele T indicated a decreased risk (OR 0.73; 95% CI 0.58-0.92) for oral cancer. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at