NM_002012.4:c.349-51129G>A

Variant names:

• chr3-59803450-C-T
• rs9846213
• NM_002012.4:c.349-51129G>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.349-51129G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.607 in 152,084 control chromosomes in the GnomAD database, including 30,686 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 0.61 (30686 hom., cov: 33)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.212
• 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002012.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	NM_002012.4	MANE Select	c.349-51129G>A		intron	N/A	NP_002003.1	P49789
	FHIT	NM_001166243.3		c.349-51129G>A		intron	N/A	NP_001159715.1	P49789
	FHIT	NM_001320899.2		c.349-51129G>A		intron	N/A	NP_001307828.1	P49789

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	ENST00000492590.6	TSL:1 MANE Select	c.349-51129G>A		intron	N/A	ENSP00000418582.1	P49789
	FHIT	ENST00000476844.5	TSL:1	c.349-51129G>A		intron	N/A	ENSP00000417557.1	P49789
	FHIT	ENST00000468189.5	TSL:2	c.349-51129G>A		intron	N/A	ENSP00000417480.1	P49789

Frequencies

GnomAD3 genomes AF: 0.607 AC: 92217 AN: 151966 Hom.: 30680 Cov.: 33

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.848

Gnomad AMR AF: 0.723

Gnomad ASJ AF: 0.815

Gnomad EAS AF: 0.555

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.733

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.607 AC: 92240 AN: 152084 Hom.: 30686 Cov.: 33 AF XY: 0.608 AC XY: 45219 AN XY: 74334

African (AFR) AF: 0.311 AC: 12920 AN: 41488

American (AMR) AF: 0.722 AC: 11043 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.815 AC: 2825 AN: 3468

East Asian (EAS) AF: 0.555 AC: 2864 AN: 5160

South Asian (SAS) AF: 0.674 AC: 3247 AN: 4816

European-Finnish (FIN) AF: 0.673 AC: 7109 AN: 10556

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.733 AC: 49860 AN: 67992

Other (OTH) AF: 0.650 AC: 1373 AN: 2112

Alfa AF: 0.681 Hom.: 76260

Bravo AF: 0.599

Asia WGS AF: 0.563 AC: 1957 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.3
DANN	Benign	0.90
PhyloP100		0.21
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: rs9846213; hg19: chr3-59789176;