3-60324697-G-T

Variant names:

• chr3-60324697-G-T
• rs1882899
• NM_002012.4:c.103+212163C>A

Variant summary

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

The NM_002012.4(FHIT):​c.103+212163C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.629 in 151,828 control chromosomes in the GnomAD database, including 30,632 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 0.63 (30632 hom., cov: 31)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.480
• 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]

LOC107986015 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.693 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.103+212163C>A		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.103+212163C>A		intron_variant	Intron 5 of 9	1	NM_002012.4	ENSP00000418582.1
FHIT	ENST00000476844.5	c.103+212163C>A		intron_variant	Intron 5 of 9	1		ENSP00000417557.1
FHIT	ENST00000468189.5	c.103+212163C>A		intron_variant	Intron 5 of 8	2		ENSP00000417480.1
FHIT	ENST00000488467.5	c.103+212163C>A		intron_variant	Intron 6 of 6	3		ENSP00000418596.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95449 AN: 151710 Hom.: 30609 Cov.: 31

Gnomad AFR AF: 0.680

Gnomad AMI AF: 0.585

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.630

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.606

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

GnomAD4 genome AF: 0.629 AC: 95522 AN: 151828 Hom.: 30632 Cov.: 31 AF XY: 0.629 AC XY: 46667 AN XY: 74180

African (AFR) AF: 0.680 AC: 28139 AN: 41390

American (AMR) AF: 0.658 AC: 10047 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.630 AC: 2185 AN: 3470

East Asian (EAS) AF: 0.210 AC: 1086 AN: 5164

South Asian (SAS) AF: 0.713 AC: 3436 AN: 4820

European-Finnish (FIN) AF: 0.614 AC: 6431 AN: 10466

Middle Eastern (MID) AF: 0.514 AC: 151 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42235 AN: 67928

Other (OTH) AF: 0.606 AC: 1280 AN: 2112

Alfa AF: 0.635 Hom.: 4327

Bravo AF: 0.628

Asia WGS AF: 0.464 AC: 1615 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.57
PhyloP100		0.48
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: rs1882899; hg19: chr3-60310427;