rs9813516

Positions:

• chr3-60307274-G-A
• chr3-60307274-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000492590.6(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 ENST00000492590.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.150

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+229586C>T		intron_variant		ENST00000492590.6	NP_002003.1
LOC107986015	XR_007095935.1	n.46738C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.103+229586C>T		intron_variant		1	NM_002012.4	ENSP00000418582	P1
FHIT	ENST00000476844.5	c.103+229586C>T		intron_variant		1		ENSP00000417557	P1
FHIT	ENST00000468189.5	c.103+229586C>T		intron_variant		2		ENSP00000417480	P1
FHIT	ENST00000488467.5	c.103+229586C>T		intron_variant		3		ENSP00000418596

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

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.542

Gnomad4 ASJ AF: 0.321

Gnomad4 EAS AF: 0.816

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.339

Gnomad4 OTH AF: 0.438

Alfa AF: 0.327 Hom.: 3438

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9813516; hg19: chr3-60293004;