rs9813516

Variant names:

• chr3-60307274-G-A
• rs9813516
• NM_002012.4:c.103+229586C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-60307274-G-A
• chr3-60307274-G-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.103+229586C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,692 control chromosomes in the GnomAD database, including 15,374 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 0.43 (15374 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150
• 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]

LOC107986015 (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 (EAS) allele frequency at 95% confidence interval = 0.796 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+229586C>T		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.103+229586C>T		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.103+229586C>T		intron_variant	Intron 5 of 9	1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.103+229586C>T		intron_variant	Intron 5 of 8	2		ENSP00000417480.1
FHIT	ENST00000488467.5	c.103+229586C>T		intron_variant	Intron 6 of 6	3		ENSP00000418596.1

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65755 AN: 151572 Hom.: 15338 Cov.: 32

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.541

Gnomad ASJ AF: 0.321

Gnomad EAS AF: 0.817

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.389

Gnomad MID AF: 0.458

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.434 AC: 65837 AN: 151692 Hom.: 15374 Cov.: 32 AF XY: 0.441 AC XY: 32674 AN XY: 74132

African (AFR) AF: 0.522 AC: 21590 AN: 41344

American (AMR) AF: 0.542 AC: 8260 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.321 AC: 1113 AN: 3466

East Asian (EAS) AF: 0.816 AC: 4196 AN: 5140

South Asian (SAS) AF: 0.455 AC: 2188 AN: 4812

European-Finnish (FIN) AF: 0.389 AC: 4089 AN: 10518

Middle Eastern (MID) AF: 0.448 AC: 130 AN: 290

European-Non Finnish (NFE) AF: 0.339 AC: 23028 AN: 67874

Other (OTH) AF: 0.438 AC: 924 AN: 2110

Alfa AF: 0.319 Hom.: 3873

Bravo AF: 0.455

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.9
DANN	Benign	0.74
PhyloP100		-0.15
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: rs9813516; hg19: chr3-60293004;