3-60324697-G-T

Position:

• chr3-60324697-G-T

Variant summary

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

The ENST00000492590.6(FHIT):​c.103+212163C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,828 control chromosomes in the GnomAD database, including 30,632 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 0.63 (30632 hom., cov: 31)
• Consequence: FHIT ENST00000492590.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480

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]

LOC107986015 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+212163C>A		intron_variant		ENST00000492590.6	NP_002003.1
LOC107986015	XR_007095935.1	n.29315C>A		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.103+212163C>A		intron_variant		1	NM_002012.4	ENSP00000418582	P1
FHIT	ENST00000476844.5	c.103+212163C>A		intron_variant		1		ENSP00000417557	P1
FHIT	ENST00000468189.5	c.103+212163C>A		intron_variant		2		ENSP00000417480	P1
FHIT	ENST00000488467.5	c.103+212163C>A		intron_variant		3		ENSP00000418596

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95449 AN: 151710 Hom.: 30609 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.629 AC: 95522 AN: 151828 Hom.: 30632 Cov.: 31 AF XY: 0.629 AC XY: 46667 AN XY: 74180

Gnomad4 AFR AF: 0.680

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.630

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.713

Gnomad4 FIN AF: 0.614

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.606

Alfa AF: 0.634 Hom.: 4142

Bravo AF: 0.628

Asia WGS AF: 0.464 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.57

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: rs1882899; hg19: chr3-60310427;