rs1735457

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_002012.4(FHIT):​c.-18+123915C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.925 in 152,280 control chromosomes in the GnomAD database, including 65,283 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 0.93 ( 65283 hom., cov: 34)

Consequence

FHIT
NM_002012.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.80
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FHITNM_002012.4 linkuse as main transcriptc.-18+123915C>T intron_variant ENST00000492590.6 NP_002003.1 P49789A0A024R366

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FHITENST00000492590.6 linkuse as main transcriptc.-18+123915C>T intron_variant 1 NM_002012.4 ENSP00000418582.1 P49789

Frequencies

GnomAD3 genomes
AF:
0.925
AC:
140807
AN:
152162
Hom.:
65227
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.932
Gnomad AMI
AF:
0.988
Gnomad AMR
AF:
0.856
Gnomad ASJ
AF:
0.895
Gnomad EAS
AF:
0.882
Gnomad SAS
AF:
0.902
Gnomad FIN
AF:
0.935
Gnomad MID
AF:
0.934
Gnomad NFE
AF:
0.941
Gnomad OTH
AF:
0.925
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.925
AC:
140922
AN:
152280
Hom.:
65283
Cov.:
34
AF XY:
0.923
AC XY:
68702
AN XY:
74450
show subpopulations
Gnomad4 AFR
AF:
0.932
Gnomad4 AMR
AF:
0.856
Gnomad4 ASJ
AF:
0.895
Gnomad4 EAS
AF:
0.883
Gnomad4 SAS
AF:
0.903
Gnomad4 FIN
AF:
0.935
Gnomad4 NFE
AF:
0.941
Gnomad4 OTH
AF:
0.926
Alfa
AF:
0.936
Hom.:
46382
Bravo
AF:
0.920
Asia WGS
AF:
0.886
AC:
3082
AN:
3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.40
CADD
Benign
13
DANN
Benign
0.62

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: rs1735457; hg19: chr3-60683737; API