rs10510860

Positions:

• chr3-61116304-G-A

Variant summary

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

The NM_002012.4(FHIT):​c.-163-74205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0916 in 151,970 control chromosomes in the GnomAD database, including 713 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 0.092 (713 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.158

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]

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 (SAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHIT	NM_002012.4	c.-163-74205C>T		intron_variant		ENST00000492590.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHIT	ENST00000492590.6	c.-163-74205C>T		intron_variant		1	NM_002012.4	P1

Frequencies

GnomAD3 genomes AF: 0.0916 AC: 13909 AN: 151850 Hom.: 709 Cov.: 32

Gnomad AFR AF: 0.0544

Gnomad AMI AF: 0.168

Gnomad AMR AF: 0.0892

Gnomad ASJ AF: 0.109

Gnomad EAS AF: 0.0187

Gnomad SAS AF: 0.198

Gnomad FIN AF: 0.0944

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.110

Gnomad OTH AF: 0.0903

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

GnomAD4 genome AF: 0.0916 AC: 13917 AN: 151970 Hom.: 713 Cov.: 32 AF XY: 0.0913 AC XY: 6777 AN XY: 74260

Gnomad4 AFR AF: 0.0544

Gnomad4 AMR AF: 0.0891

Gnomad4 ASJ AF: 0.109

Gnomad4 EAS AF: 0.0188

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.0944

Gnomad4 NFE AF: 0.110

Gnomad4 OTH AF: 0.0932

Alfa AF: 0.112 Hom.: 508

Bravo AF: 0.0874

Asia WGS AF: 0.127 AC: 442 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.82

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: rs10510860; hg19: chr3-61101977;