NM_002012.4:c.104-247241C>A

Variant names:

• chr3-60261393-G-T
• rs10510835
• NM_002012.4:c.104-247241C>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.104-247241C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 151,882 control chromosomes in the GnomAD database, including 2,749 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 0.17 (2749 hom., cov: 31)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.880
• Publications: 3 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]

LOC107986015 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.104-247241C>A		intron_variant	Intron 5 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.104-247241C>A		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.104-247241C>A		intron_variant	Intron 5 of 9	1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.104-247241C>A		intron_variant	Intron 5 of 8	2		ENSP00000417480.1
FHIT	ENST00000488467.5	c.104-247241C>A		intron_variant	Intron 6 of 6	3		ENSP00000418596.1

Frequencies

GnomAD3 genomes AF: 0.172 AC: 26178 AN: 151764 Hom.: 2753 Cov.: 31

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.237

Gnomad EAS AF: 0.00852

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.243

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.172 AC: 26158 AN: 151882 Hom.: 2749 Cov.: 31 AF XY: 0.168 AC XY: 12478 AN XY: 74222

African (AFR) AF: 0.0734 AC: 3044 AN: 41478

American (AMR) AF: 0.160 AC: 2433 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.237 AC: 818 AN: 3450

East Asian (EAS) AF: 0.00834 AC: 43 AN: 5154

South Asian (SAS) AF: 0.126 AC: 607 AN: 4808

European-Finnish (FIN) AF: 0.194 AC: 2045 AN: 10560

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.244 AC: 16532 AN: 67890

Other (OTH) AF: 0.202 AC: 425 AN: 2108

Alfa AF: 0.178 Hom.: 2745

Bravo AF: 0.166

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.10
DANN	Benign	0.49
PhyloP100		-0.88
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: rs10510835; hg19: chr3-60247121;