3-59803888-G-T

Variant names:

• chr3-59803888-G-T
• rs534185
• NM_002012.4:c.349-51567C>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.349-51567C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 151,992 control chromosomes in the GnomAD database, including 49,429 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 0.80 (49429 hom., cov: 31)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.58
• 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]

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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.861 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	NM_002012.4	MANE Select	c.349-51567C>A		intron	N/A	NP_002003.1
	FHIT	NM_001166243.3		c.349-51567C>A		intron	N/A	NP_001159715.1
	FHIT	NM_001320899.2		c.349-51567C>A		intron	N/A	NP_001307828.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FHIT	ENST00000492590.6	TSL:1 MANE Select	c.349-51567C>A		intron	N/A	ENSP00000418582.1
	FHIT	ENST00000476844.5	TSL:1	c.349-51567C>A		intron	N/A	ENSP00000417557.1
	FHIT	ENST00000468189.5	TSL:2	c.349-51567C>A		intron	N/A	ENSP00000417480.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121617 AN: 151874 Hom.: 49403 Cov.: 31

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.979

Gnomad AMR AF: 0.855

Gnomad ASJ AF: 0.912

Gnomad EAS AF: 0.563

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.791

Gnomad MID AF: 0.927

Gnomad NFE AF: 0.866

Gnomad OTH AF: 0.835

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

GnomAD4 genome AF: 0.801 AC: 121690 AN: 151992 Hom.: 49429 Cov.: 31 AF XY: 0.798 AC XY: 59260 AN XY: 74266

African (AFR) AF: 0.693 AC: 28737 AN: 41458

American (AMR) AF: 0.854 AC: 13028 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 3161 AN: 3466

East Asian (EAS) AF: 0.562 AC: 2894 AN: 5146

South Asian (SAS) AF: 0.768 AC: 3688 AN: 4802

European-Finnish (FIN) AF: 0.791 AC: 8369 AN: 10578

Middle Eastern (MID) AF: 0.932 AC: 274 AN: 294

European-Non Finnish (NFE) AF: 0.866 AC: 58889 AN: 67970

Other (OTH) AF: 0.834 AC: 1759 AN: 2108

Alfa AF: 0.856 Hom.: 69412

Bravo AF: 0.803

Asia WGS AF: 0.635 AC: 2208 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.075
DANN	Benign	0.54
PhyloP100		-2.6
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: rs534185; hg19: chr3-59789614;