rs13059601

Positions:

• chr3-60419271-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002012.4(FHIT):​c.103+117589G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,208 control chromosomes in the GnomAD database, including 2,143 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 0.14 (2143 hom., cov: 33)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+117589G>A		intron_variant		ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.103+117589G>A		intron_variant		1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.103+117589G>A		intron_variant		1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.103+117589G>A		intron_variant		2		ENSP00000417480.1
FHIT	ENST00000488467.5	c.103+117589G>A		intron_variant		3		ENSP00000418596.1

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20596 AN: 152090 Hom.: 2133 Cov.: 33

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0474

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.0516

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.136 AC: 20642 AN: 152208 Hom.: 2143 Cov.: 33 AF XY: 0.139 AC XY: 10377 AN XY: 74426

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.104

Gnomad4 EAS AF: 0.242

Gnomad4 SAS AF: 0.227

Gnomad4 FIN AF: 0.0474

Gnomad4 NFE AF: 0.0516

Gnomad4 OTH AF: 0.125

Alfa AF: 0.0766 Hom.: 980

Bravo AF: 0.154

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.72

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

Publications

LitVar

Other links and lift over

dbSNP: rs13059601; hg19: chr3-60405004;