rs7617530

Positions:

• chr3-60600023-G-A
• chr3-60600023-G-T

Variant summary

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

The NM_002012.4(FHIT):​c.-17-63044C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.271 in 151,906 control chromosomes in the GnomAD database, including 6,195 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 0.27 (6195 hom., cov: 31)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.357

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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FHIT	NM_002012.4	c.-17-63044C>T		intron_variant		ENST00000492590.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FHIT	ENST00000492590.6	c.-17-63044C>T		intron_variant		1	NM_002012.4	P1

Frequencies

GnomAD3 genomes AF: 0.271 AC: 41206 AN: 151786 Hom.: 6192 Cov.: 31

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.268

Gnomad EAS AF: 0.568

Gnomad SAS AF: 0.464

Gnomad FIN AF: 0.276

Gnomad MID AF: 0.150

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.266

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

GnomAD4 genome AF: 0.271 AC: 41225 AN: 151906 Hom.: 6195 Cov.: 31 AF XY: 0.274 AC XY: 20310 AN XY: 74220

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.268

Gnomad4 EAS AF: 0.569

Gnomad4 SAS AF: 0.462

Gnomad4 FIN AF: 0.276

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.271

Alfa AF: 0.291 Hom.: 3136

Bravo AF: 0.264

Asia WGS AF: 0.525 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.39
DANN	Benign	0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs7617530; hg19: chr3-60585756;