rs643629

Variant names:

• chr3-59905250-G-A
• rs643629
• NM_002012.4:c.348+17096C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002012.4(FHIT):​c.348+17096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,176 control chromosomes in the GnomAD database, including 839 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 0.10 (839 hom., cov: 33)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 5 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]

LOC105377113 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.121 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.348+17096C>T		intron	N/A	NP_002003.1	P49789
	FHIT	NM_001166243.3		c.348+17096C>T		intron	N/A	NP_001159715.1	P49789
	FHIT	NM_001320899.2		c.348+17096C>T		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.348+17096C>T		intron	N/A	ENSP00000418582.1	P49789
	FHIT	ENST00000476844.5	TSL:1	c.348+17096C>T		intron	N/A	ENSP00000417557.1	P49789
	FHIT	ENST00000468189.5	TSL:2	c.348+17096C>T		intron	N/A	ENSP00000417480.1	P49789

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15784 AN: 152058 Hom.: 840 Cov.: 33

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.104 AC: 15779 AN: 152176 Hom.: 839 Cov.: 33 AF XY: 0.101 AC XY: 7542 AN XY: 74418

African (AFR) AF: 0.0734 AC: 3047 AN: 41524

American (AMR) AF: 0.0813 AC: 1243 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 426 AN: 3466

East Asian (EAS) AF: 0.111 AC: 572 AN: 5172

South Asian (SAS) AF: 0.106 AC: 510 AN: 4826

European-Finnish (FIN) AF: 0.100 AC: 1058 AN: 10582

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.123 AC: 8379 AN: 67996

Other (OTH) AF: 0.111 AC: 235 AN: 2110

Alfa AF: 0.114 Hom.: 1747

Bravo AF: 0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.42
PhyloP100		-0.0090
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: rs643629; hg19: chr3-59890976;