rs3845972

Variant names:

• chr3-60042108-G-A
• rs3845972
• NM_002012.4:c.104-27956C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-60042108-G-A
• chr3-60042108-G-C

Variant summary

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

The NM_002012.4(FHIT):​c.104-27956C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 152,016 control chromosomes in the GnomAD database, including 24,613 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 0.56 (24613 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 5 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.104-27956C>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.104-27956C>T		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.562 AC: 85298 AN: 151898 Hom.: 24589 Cov.: 32

Gnomad AFR AF: 0.506

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.265

Gnomad SAS AF: 0.439

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.760

Gnomad NFE AF: 0.639

Gnomad OTH AF: 0.590

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

GnomAD4 genome AF: 0.562 AC: 85361 AN: 152016 Hom.: 24613 Cov.: 32 AF XY: 0.557 AC XY: 41365 AN XY: 74294

African (AFR) AF: 0.506 AC: 20993 AN: 41454

American (AMR) AF: 0.462 AC: 7052 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2027 AN: 3466

East Asian (EAS) AF: 0.265 AC: 1367 AN: 5152

South Asian (SAS) AF: 0.439 AC: 2114 AN: 4816

European-Finnish (FIN) AF: 0.608 AC: 6403 AN: 10538

Middle Eastern (MID) AF: 0.766 AC: 222 AN: 290

European-Non Finnish (NFE) AF: 0.639 AC: 43485 AN: 68002

Other (OTH) AF: 0.584 AC: 1234 AN: 2112

Alfa AF: 0.587 Hom.: 13683

Bravo AF: 0.551

Asia WGS AF: 0.358 AC: 1243 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.6
DANN	Benign	0.74
PhyloP100		-0.034
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: rs3845972; hg19: chr3-60027834;