3-60054286-C-T

Variant names:

• chr3-60054286-C-T
• rs9311746
• NM_002012.4:c.104-40134G>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.104-40134G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,022 control chromosomes in the GnomAD database, including 20,324 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 0.51 (20324 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990
• 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]

ENSG00000299700 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.104-40134G>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.104-40134G>A		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 77925 AN: 151904 Hom.: 20314 Cov.: 32

Gnomad AFR AF: 0.544

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.539

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.513 AC: 77971 AN: 152022 Hom.: 20324 Cov.: 32 AF XY: 0.509 AC XY: 37819 AN XY: 74332

African (AFR) AF: 0.544 AC: 22563 AN: 41460

American (AMR) AF: 0.424 AC: 6476 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1581 AN: 3464

East Asian (EAS) AF: 0.263 AC: 1361 AN: 5182

South Asian (SAS) AF: 0.430 AC: 2075 AN: 4826

European-Finnish (FIN) AF: 0.532 AC: 5603 AN: 10540

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.539 AC: 36616 AN: 67950

Other (OTH) AF: 0.522 AC: 1104 AN: 2114

Alfa AF: 0.527 Hom.: 12407

Bravo AF: 0.510

Asia WGS AF: 0.344 AC: 1198 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		0.099
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: rs9311746; hg19: chr3-60040012;