3-60189317-C-T

Variant names:

• chr3-60189317-C-T
• rs384530
• NM_002012.4:c.104-175165G>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.104-175165G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.714 in 152,012 control chromosomes in the GnomAD database, including 39,034 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 0.71 (39034 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.181
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.904 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	NM_002012.4	MANE Select	c.104-175165G>A		intron	N/A	NP_002003.1	P49789
	FHIT	NM_001166243.3		c.104-175165G>A		intron	N/A	NP_001159715.1	P49789
	FHIT	NM_001320899.2		c.104-175165G>A		intron	N/A	NP_001307828.1	P49789

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	ENST00000492590.6	TSL:1 MANE Select	c.104-175165G>A		intron	N/A	ENSP00000418582.1	P49789
	FHIT	ENST00000476844.5	TSL:1	c.104-175165G>A		intron	N/A	ENSP00000417557.1	P49789
	FHIT	ENST00000468189.5	TSL:2	c.104-175165G>A		intron	N/A	ENSP00000417480.1	P49789

Frequencies

GnomAD3 genomes AF: 0.714 AC: 108491 AN: 151894 Hom.: 39007 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.777

Gnomad ASJ AF: 0.756

Gnomad EAS AF: 0.927

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.668

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.709

Gnomad OTH AF: 0.717

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

GnomAD4 genome AF: 0.714 AC: 108571 AN: 152012 Hom.: 39034 Cov.: 32 AF XY: 0.716 AC XY: 53221 AN XY: 74304

African (AFR) AF: 0.673 AC: 27913 AN: 41448

American (AMR) AF: 0.778 AC: 11884 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.756 AC: 2613 AN: 3456

East Asian (EAS) AF: 0.926 AC: 4795 AN: 5176

South Asian (SAS) AF: 0.757 AC: 3651 AN: 4822

European-Finnish (FIN) AF: 0.668 AC: 7046 AN: 10548

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.709 AC: 48221 AN: 67970

Other (OTH) AF: 0.718 AC: 1514 AN: 2108

Alfa AF: 0.709 Hom.: 23153

Bravo AF: 0.720

Asia WGS AF: 0.802 AC: 2790 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.44
DANN	Benign	0.58
PhyloP100		0.18
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: rs384530; hg19: chr3-60175045;