3-60522607-G-T

Variant names:

• chr3-60522607-G-T
• rs80171647
• NM_002012.4:c.103+14253C>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.103+14253C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0717 in 152,208 control chromosomes in the GnomAD database, including 544 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 0.072 (544 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+14253C>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.103+14253C>A		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.103+14253C>A		intron_variant	Intron 5 of 9	1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.103+14253C>A		intron_variant	Intron 5 of 8	2		ENSP00000417480.1
FHIT	ENST00000488467.5	c.103+14253C>A		intron_variant	Intron 6 of 6	3		ENSP00000418596.1

Frequencies

GnomAD3 genomes AF: 0.0717 AC: 10898 AN: 152090 Hom.: 544 Cov.: 32

Gnomad AFR AF: 0.0638

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0548

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.0420

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0770

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

GnomAD4 genome AF: 0.0717 AC: 10908 AN: 152208 Hom.: 544 Cov.: 32 AF XY: 0.0756 AC XY: 5624 AN XY: 74430

African (AFR) AF: 0.0640 AC: 2656 AN: 41510

American (AMR) AF: 0.141 AC: 2161 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0548 AC: 190 AN: 3470

East Asian (EAS) AF: 0.140 AC: 727 AN: 5176

South Asian (SAS) AF: 0.194 AC: 934 AN: 4812

European-Finnish (FIN) AF: 0.0420 AC: 445 AN: 10606

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3603 AN: 68024

Other (OTH) AF: 0.0777 AC: 164 AN: 2112

Alfa AF: 0.0572 Hom.: 498

Bravo AF: 0.0761

Asia WGS AF: 0.180 AC: 626 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.34
PhyloP100		-0.018
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: rs80171647; hg19: chr3-60508340;