3-60803137-T-C

Variant names:

• chr3-60803137-T-C
• rs1447925
• NM_002012.4:c.-18+18782A>G

Variant summary

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

The NM_002012.4(FHIT):​c.-18+18782A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.669 in 152,072 control chromosomes in the GnomAD database, including 36,274 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 0.67 (36274 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.-18+18782A>G		intron_variant	Intron 4 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.-18+18782A>G		intron_variant	Intron 4 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.670 AC: 101743 AN: 151954 Hom.: 36282 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.803

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.798

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.731

Gnomad FIN AF: 0.758

Gnomad MID AF: 0.804

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.669 AC: 101764 AN: 152072 Hom.: 36274 Cov.: 32 AF XY: 0.671 AC XY: 49883 AN XY: 74342

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.714

Gnomad4 ASJ AF: 0.798

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.731

Gnomad4 FIN AF: 0.758

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.718

Alfa AF: 0.776 Hom.: 61809

Bravo AF: 0.669

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1447925; hg19: chr3-60788842;