rs643629

Positions:

• chr3-59905250-G-A

Variant summary

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

The ENST00000492590.6(FHIT):​c.348+17096C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,176 control chromosomes in the GnomAD database, including 839 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 0.10 (839 hom., cov: 33)
• Consequence: FHIT ENST00000492590.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900

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]

LOC105377113 (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 (NFE) allele frequency at 95% confidence interval = 0.121 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIT	NM_002012.4	c.348+17096C>T		intron_variant		ENST00000492590.6	NP_002003.1
LOC105377113	XR_007095936.1	n.26562G>A		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.348+17096C>T		intron_variant		1	NM_002012.4	ENSP00000418582	P1
FHIT	ENST00000476844.5	c.348+17096C>T		intron_variant		1		ENSP00000417557	P1
FHIT	ENST00000468189.5	c.348+17096C>T		intron_variant		2		ENSP00000417480	P1
FHIT	ENST00000466788.1	n.375+17096C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15784 AN: 152058 Hom.: 840 Cov.: 33

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.302

Gnomad AMR AF: 0.0814

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.100

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.123

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.104 AC: 15779 AN: 152176 Hom.: 839 Cov.: 33 AF XY: 0.101 AC XY: 7542 AN XY: 74418

Gnomad4 AFR AF: 0.0734

Gnomad4 AMR AF: 0.0813

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.106

Gnomad4 FIN AF: 0.100

Gnomad4 NFE AF: 0.123

Gnomad4 OTH AF: 0.111

Alfa AF: 0.117 Hom.: 1413

Bravo AF: 0.100

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.42

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: rs643629; hg19: chr3-59890976;