rs213376

Positions:

• chr3-60288320-G-A

Variant summary

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

The NM_002012.4(FHIT):​c.103+248540C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 151,890 control chromosomes in the GnomAD database, including 12,089 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 0.38 (12089 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.158

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+248540C>T		intron_variant		ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.103+248540C>T		intron_variant		1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.103+248540C>T		intron_variant		1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.103+248540C>T		intron_variant		2		ENSP00000417480.1
FHIT	ENST00000488467.5	c.103+248540C>T		intron_variant		3		ENSP00000418596.1

Frequencies

GnomAD3 genomes AF: 0.383 AC: 58075 AN: 151772 Hom.: 12089 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.0387

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.427

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.382 AC: 58093 AN: 151890 Hom.: 12089 Cov.: 32 AF XY: 0.378 AC XY: 28028 AN XY: 74210

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.322

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.0386

Gnomad4 SAS AF: 0.433

Gnomad4 FIN AF: 0.427

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.424

Alfa AF: 0.453 Hom.: 19629

Bravo AF: 0.365

Asia WGS AF: 0.225 AC: 783 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.55

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: rs213376; hg19: chr3-60274049;