rs17361653

Variant names:

• chr3-59785789-G-A
• rs17361653
• NM_002012.4:c.349-33468C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002012.4(FHIT):​c.349-33468C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.478 in 152,012 control chromosomes in the GnomAD database, including 17,638 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 0.48 (17638 hom., cov: 33)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.682
• Publications: 2 publications found

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]

CFAP20DC-DT (HGNC:55618): (CFAP20DC divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.349-33468C>T		intron_variant	Intron 8 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.349-33468C>T		intron_variant	Intron 8 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.478 AC: 72625 AN: 151894 Hom.: 17629 Cov.: 33

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.503

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.496

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

GnomAD4 genome AF: 0.478 AC: 72667 AN: 152012 Hom.: 17638 Cov.: 33 AF XY: 0.477 AC XY: 35411 AN XY: 74304

African (AFR) AF: 0.407 AC: 16863 AN: 41452

American (AMR) AF: 0.503 AC: 7690 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1943 AN: 3470

East Asian (EAS) AF: 0.427 AC: 2208 AN: 5168

South Asian (SAS) AF: 0.333 AC: 1606 AN: 4818

European-Finnish (FIN) AF: 0.594 AC: 6276 AN: 10560

Middle Eastern (MID) AF: 0.497 AC: 145 AN: 292

European-Non Finnish (NFE) AF: 0.508 AC: 34506 AN: 67942

Other (OTH) AF: 0.497 AC: 1050 AN: 2112

Alfa AF: 0.496 Hom.: 23964

Bravo AF: 0.470

Asia WGS AF: 0.374 AC: 1299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.74
DANN	Benign	0.73
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17361653; hg19: chr3-59771515;