rs9874888

Variant names:

• chr3-60030591-T-A
• rs9874888
• NM_002012.4:c.104-16439A>T

Your query was ambiguous. Multiple possible variants found:

• chr3-60030591-T-A
• chr3-60030591-T-G

Variant summary

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

The NM_002012.4(FHIT):​c.104-16439A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,072 control chromosomes in the GnomAD database, including 6,996 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 0.30 (6996 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.236
• Publications: 4 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.104-16439A>T		intron_variant	Intron 5 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.104-16439A>T		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.299 AC: 45454 AN: 151954 Hom.: 6993 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.364

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.299 AC: 45493 AN: 152072 Hom.: 6996 Cov.: 32 AF XY: 0.302 AC XY: 22466 AN XY: 74334

African (AFR) AF: 0.322 AC: 13347 AN: 41478

American (AMR) AF: 0.256 AC: 3915 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 1262 AN: 3468

East Asian (EAS) AF: 0.474 AC: 2441 AN: 5154

South Asian (SAS) AF: 0.379 AC: 1828 AN: 4822

European-Finnish (FIN) AF: 0.319 AC: 3375 AN: 10568

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18448 AN: 67978

Other (OTH) AF: 0.277 AC: 586 AN: 2114

Alfa AF: 0.300 Hom.: 854

Bravo AF: 0.298

Asia WGS AF: 0.406 AC: 1410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.80
DANN	Benign	0.72
PhyloP100		-0.24
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: rs9874888; hg19: chr3-60016317;