3-59917075-C-T

Variant names:

• chr3-59917075-C-T
• rs1825630
• NM_002012.4:c.348+5271G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_002012.4(FHIT):​c.348+5271G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 152,152 control chromosomes in the GnomAD database, including 15,894 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 0.45 (15894 hom., cov: 33)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.895
• Publications: 10 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.348+5271G>A		intron_variant	Intron 8 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.348+5271G>A		intron_variant	Intron 8 of 9	1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.348+5271G>A		intron_variant	Intron 8 of 9	1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.348+5271G>A		intron_variant	Intron 8 of 8	2		ENSP00000417480.1
FHIT	ENST00000466788.1	n.375+5271G>A		intron_variant	Intron 5 of 6	4

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68945 AN: 152034 Hom.: 15889 Cov.: 33

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.537

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.502

Gnomad SAS AF: 0.447

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.473

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

GnomAD4 genome AF: 0.453 AC: 68987 AN: 152152 Hom.: 15894 Cov.: 33 AF XY: 0.452 AC XY: 33614 AN XY: 74390

African (AFR) AF: 0.438 AC: 18173 AN: 41502

American (AMR) AF: 0.375 AC: 5732 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1662 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2593 AN: 5174

South Asian (SAS) AF: 0.450 AC: 2163 AN: 4812

European-Finnish (FIN) AF: 0.414 AC: 4377 AN: 10574

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.480 AC: 32655 AN: 68006

Other (OTH) AF: 0.474 AC: 1001 AN: 2112

Alfa AF: 0.473 Hom.: 37228

Bravo AF: 0.451

Asia WGS AF: 0.471 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.78
PhyloP100		0.90
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: rs1825630; hg19: chr3-59902801;