3-60113429-A-G

Variant names:

• chr3-60113429-A-G
• rs760317
• NM_002012.4:c.104-99277T>C

Variant summary

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

The NM_002012.4(FHIT):​c.104-99277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.6 in 151,652 control chromosomes in the GnomAD database, including 27,995 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 0.60 (27995 hom., cov: 31)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391
• Publications: 4 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]

ENSG00000299680 (HGNC:):

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 (AFR) allele frequency at 95% confidence interval = 0.702 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.104-99277T>C		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.104-99277T>C		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 90877 AN: 151534 Hom.: 27970 Cov.: 31

Gnomad AFR AF: 0.709

Gnomad AMI AF: 0.480

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.455

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.702

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.532

Gnomad NFE AF: 0.543

Gnomad OTH AF: 0.543

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

GnomAD4 genome AF: 0.600 AC: 90954 AN: 151652 Hom.: 27995 Cov.: 31 AF XY: 0.603 AC XY: 44715 AN XY: 74112

African (AFR) AF: 0.709 AC: 29157 AN: 41150

American (AMR) AF: 0.570 AC: 8698 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.455 AC: 1572 AN: 3452

East Asian (EAS) AF: 0.697 AC: 3596 AN: 5156

South Asian (SAS) AF: 0.702 AC: 3379 AN: 4812

European-Finnish (FIN) AF: 0.559 AC: 5902 AN: 10554

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.543 AC: 36908 AN: 67952

Other (OTH) AF: 0.548 AC: 1152 AN: 2104

Alfa AF: 0.482 Hom.: 1469

Bravo AF: 0.599

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
DANN	Benign	0.60
PhyloP100		-0.39
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: rs760317; hg19: chr3-60099156;