chr3-60912762-T-C

Variant names:

• chr3-60912762-T-C
• rs11130795
• NM_002012.4:c.-110-90751A>G

Variant summary

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

The NM_002012.4(FHIT):​c.-110-90751A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 514,662 control chromosomes in the GnomAD database, including 49,513 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 0.35 (11558 hom., cov: 32)
  • Exomes 𝑓: 0.44 (37955 hom.)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.-110-90751A>G		intron_variant	Intron 3 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.-110-90751A>G		intron_variant	Intron 3 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.349 AC: 53115 AN: 151984 Hom.: 11554 Cov.: 32

Gnomad AFR AF: 0.122

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.408

Gnomad OTH AF: 0.319

GnomAD3 exomes AF: 0.446 AC: 100817 AN: 225798 Hom.: 25860 AF XY: 0.442 AC XY: 55152 AN XY: 124848

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.593

Gnomad ASJ exome AF: 0.239

Gnomad EAS exome AF: 0.834

Gnomad SAS exome AF: 0.473

Gnomad FIN exome AF: 0.444

Gnomad NFE exome AF: 0.396

Gnomad OTH exome AF: 0.405

GnomAD4 exome AF: 0.437 AC: 158498 AN: 362560 Hom.: 37955 Cov.: 0 AF XY: 0.436 AC XY: 90705 AN XY: 207920

Gnomad4 AFR exome AF: 0.114

Gnomad4 AMR exome AF: 0.591

Gnomad4 ASJ exome AF: 0.238

Gnomad4 EAS exome AF: 0.838

Gnomad4 SAS exome AF: 0.470

Gnomad4 FIN exome AF: 0.443

Gnomad4 NFE exome AF: 0.405

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.349 AC: 53138 AN: 152102 Hom.: 11558 Cov.: 32 AF XY: 0.359 AC XY: 26695 AN XY: 74362

Gnomad4 AFR AF: 0.122

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.833

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.408

Gnomad4 OTH AF: 0.322

Alfa AF: 0.377 Hom.: 2746

Bravo AF: 0.340

Asia WGS AF: 0.588 AC: 2041 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.79

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: rs11130795; hg19: chr3-60898434;