chr3-60479546-G-A

Variant names:

• chr3-60479546-G-A
• rs1447971
• NM_002012.4:c.103+57314C>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.103+57314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,070 control chromosomes in the GnomAD database, including 17,486 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 0.45 (17486 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01
• Publications: 6 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.658 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+57314C>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.103+57314C>T		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.103+57314C>T		intron_variant	Intron 5 of 9	1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.103+57314C>T		intron_variant	Intron 5 of 8	2		ENSP00000417480.1
FHIT	ENST00000488467.5	c.103+57314C>T		intron_variant	Intron 6 of 6	3		ENSP00000418596.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68992 AN: 151952 Hom.: 17436 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.387

Gnomad EAS AF: 0.548

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.481

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

GnomAD4 genome AF: 0.454 AC: 69100 AN: 152070 Hom.: 17486 Cov.: 32 AF XY: 0.452 AC XY: 33641 AN XY: 74358

African (AFR) AF: 0.665 AC: 27560 AN: 41460

American (AMR) AF: 0.505 AC: 7717 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 1343 AN: 3466

East Asian (EAS) AF: 0.548 AC: 2824 AN: 5154

South Asian (SAS) AF: 0.577 AC: 2786 AN: 4830

European-Finnish (FIN) AF: 0.219 AC: 2319 AN: 10602

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.340 AC: 23119 AN: 67966

Other (OTH) AF: 0.484 AC: 1024 AN: 2116

Alfa AF: 0.389 Hom.: 21451

Bravo AF: 0.483

Asia WGS AF: 0.583 AC: 2021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.34
DANN	Benign	0.24
PhyloP100		-1.0
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: rs1447971; hg19: chr3-60465279;