3-60527156-A-G

Variant names:

• chr3-60527156-A-G
• rs241704
• NM_002012.4:c.103+9704T>C

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+9704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,972 control chromosomes in the GnomAD database, including 28,757 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 0.61 (28757 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+9704T>C		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+9704T>C		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.103+9704T>C		intron_variant	Intron 5 of 9	1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.103+9704T>C		intron_variant	Intron 5 of 8	2		ENSP00000417480.1
FHIT	ENST00000488467.5	c.103+9704T>C		intron_variant	Intron 6 of 6	3		ENSP00000418596.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92992 AN: 151854 Hom.: 28749 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.544

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.615

Gnomad OTH AF: 0.572

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

GnomAD4 genome AF: 0.612 AC: 93049 AN: 151972 Hom.: 28757 Cov.: 32 AF XY: 0.609 AC XY: 45252 AN XY: 74280

African (AFR) AF: 0.612 AC: 25356 AN: 41432

American (AMR) AF: 0.628 AC: 9597 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1650 AN: 3466

East Asian (EAS) AF: 0.735 AC: 3791 AN: 5160

South Asian (SAS) AF: 0.662 AC: 3179 AN: 4800

European-Finnish (FIN) AF: 0.544 AC: 5739 AN: 10546

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.615 AC: 41826 AN: 67980

Other (OTH) AF: 0.571 AC: 1206 AN: 2112

Alfa AF: 0.611 Hom.: 55433

Bravo AF: 0.621

Asia WGS AF: 0.707 AC: 2459 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.6
DANN	Benign	0.65
PhyloP100		-0.053
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: rs241704; hg19: chr3-60512889;