rs2736779

Variant names:

• chr3-60081118-G-A
• rs2736779
• NM_002012.4:c.104-66966C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-60081118-G-A
• chr3-60081118-G-C
• chr3-60081118-G-T

Variant summary

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

The NM_002012.4(FHIT):​c.104-66966C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 151,906 control chromosomes in the GnomAD database, including 11,672 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 0.38 (11672 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.218
• 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]

ENSG00000299680 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.104-66966C>T		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.104-66966C>T		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57891 AN: 151788 Hom.: 11670 Cov.: 32

Gnomad AFR AF: 0.509

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.340

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.354

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.318

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.381 AC: 57908 AN: 151906 Hom.: 11672 Cov.: 32 AF XY: 0.383 AC XY: 28436 AN XY: 74262

African (AFR) AF: 0.509 AC: 21074 AN: 41426

American (AMR) AF: 0.340 AC: 5183 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1438 AN: 5154

South Asian (SAS) AF: 0.453 AC: 2184 AN: 4820

European-Finnish (FIN) AF: 0.354 AC: 3739 AN: 10564

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.318 AC: 21585 AN: 67916

Other (OTH) AF: 0.359 AC: 757 AN: 2108

Alfa AF: 0.351 Hom.: 3670

Bravo AF: 0.384

Asia WGS AF: 0.370 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.6
DANN	Benign	0.33
PhyloP100		0.22
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: rs2736779; hg19: chr3-60066844;