rs13059601

Variant names:

• chr3-60419271-C-T
• rs13059601
• NM_002012.4:c.103+117589G>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+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
• Publications: 1 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	NM_002012.4	MANE Select	c.103+117589G>A		intron	N/A	NP_002003.1
	FHIT	NM_001166243.3		c.103+117589G>A		intron	N/A	NP_001159715.1
	FHIT	NM_001320899.2		c.103+117589G>A		intron	N/A	NP_001307828.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	ENST00000492590.6	TSL:1 MANE Select	c.103+117589G>A		intron	N/A	ENSP00000418582.1
	FHIT	ENST00000476844.5	TSL:1	c.103+117589G>A		intron	N/A	ENSP00000417557.1
	FHIT	ENST00000468189.5	TSL:2	c.103+117589G>A		intron	N/A	ENSP00000417480.1

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

African (AFR) AF: 0.235 AC: 9756 AN: 41516

American (AMR) AF: 0.250 AC: 3829 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 360 AN: 3468

East Asian (EAS) AF: 0.242 AC: 1250 AN: 5170

South Asian (SAS) AF: 0.227 AC: 1097 AN: 4824

European-Finnish (FIN) AF: 0.0474 AC: 503 AN: 10606

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.0516 AC: 3507 AN: 68020

Other (OTH) AF: 0.125 AC: 263 AN: 2112

Alfa AF: 0.0852 Hom.: 1559

Bravo AF: 0.154

Asia WGS AF: 0.266 AC: 926 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.66
DANN	Benign	0.72
PhyloP100		-0.76
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: rs13059601; hg19: chr3-60405004;