3-60112188-C-T

Variant names:

• chr3-60112188-C-T
• rs9814915
• NM_002012.4:c.104-98036G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.658
• Publications: 2 publications found

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]

ENSG00000299680 (HGNC:):

ACMG classification

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
FHIT	NM_002012.4	c.104-98036G>A		intron_variant	Intron 5 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.104-98036G>A		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109321 AN: 151866 Hom.: 39616 Cov.: 31

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

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

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

Other links and lift over

dbSNP: rs9814915; hg19: chr3-60097915;