rs722070

Variant names:

• chr3-60126568-G-A
• rs722070
• NM_002012.4:c.104-112416C>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.104-112416C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,934 control chromosomes in the GnomAD database, including 15,323 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 0.44 (15323 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.434
• Publications: 3 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]

ENSG00000299680 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.476 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.104-112416C>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.104-112416C>T		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67489 AN: 151816 Hom.: 15320 Cov.: 32

Gnomad AFR AF: 0.482

Gnomad AMI AF: 0.469

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.444

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.442

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.444 AC: 67518 AN: 151934 Hom.: 15323 Cov.: 32 AF XY: 0.444 AC XY: 32924 AN XY: 74226

African (AFR) AF: 0.481 AC: 19938 AN: 41426

American (AMR) AF: 0.331 AC: 5065 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1374 AN: 3456

East Asian (EAS) AF: 0.254 AC: 1309 AN: 5160

South Asian (SAS) AF: 0.445 AC: 2147 AN: 4828

European-Finnish (FIN) AF: 0.465 AC: 4899 AN: 10530

Middle Eastern (MID) AF: 0.438 AC: 127 AN: 290

European-Non Finnish (NFE) AF: 0.462 AC: 31381 AN: 67940

Other (OTH) AF: 0.403 AC: 850 AN: 2110

Alfa AF: 0.450 Hom.: 22761

Bravo AF: 0.429

Asia WGS AF: 0.325 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.24
DANN	Benign	0.44
PhyloP100		-0.43
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: rs722070; hg19: chr3-60112295;