chr3-60949298-T-C

Variant names:

• chr3-60949298-T-C
• rs17684830
• NM_002012.4:c.-111+92749A>G

Variant summary

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

The NM_002012.4(FHIT):​c.-111+92749A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,214 control chromosomes in the GnomAD database, including 1,635 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 0.13 (1635 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0570
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.-111+92749A>G		intron_variant	Intron 3 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.-111+92749A>G		intron_variant	Intron 3 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19335 AN: 152096 Hom.: 1637 Cov.: 32

Gnomad AFR AF: 0.0366

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.00752

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.208

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.129

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19334 AN: 152214 Hom.: 1635 Cov.: 32 AF XY: 0.125 AC XY: 9286 AN XY: 74398

African (AFR) AF: 0.0367 AC: 1524 AN: 41570

American (AMR) AF: 0.107 AC: 1634 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 537 AN: 3470

East Asian (EAS) AF: 0.00773 AC: 40 AN: 5174

South Asian (SAS) AF: 0.167 AC: 808 AN: 4832

European-Finnish (FIN) AF: 0.208 AC: 2200 AN: 10578

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12010 AN: 67974

Other (OTH) AF: 0.129 AC: 273 AN: 2112

Alfa AF: 0.160 Hom.: 1060

Bravo AF: 0.114

Asia WGS AF: 0.111 AC: 388 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.65
PhyloP100		0.057
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: rs17684830; hg19: chr3-60934970;