rs9311796

Variant names:

• chr3-61128483-A-C
• rs9311796
• NM_002012.4:c.-164+72134T>G

Variant summary

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

The NM_002012.4(FHIT):​c.-164+72134T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 152,094 control chromosomes in the GnomAD database, including 1,597 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 0.14 (1597 hom., cov: 32)
• Consequence: FHIT NM_002012.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.48
• 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FHIT	NM_002012.4	c.-164+72134T>G		intron_variant	Intron 2 of 9	ENST00000492590.6	NP_002003.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FHIT	ENST00000492590.6	c.-164+72134T>G		intron_variant	Intron 2 of 9	1	NM_002012.4	ENSP00000418582.1

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20769 AN: 151976 Hom.: 1582 Cov.: 32

Gnomad AFR AF: 0.212

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.0407

Gnomad EAS AF: 0.0934

Gnomad SAS AF: 0.0471

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.113

Gnomad OTH AF: 0.122

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

GnomAD4 genome AF: 0.137 AC: 20812 AN: 152094 Hom.: 1597 Cov.: 32 AF XY: 0.136 AC XY: 10099 AN XY: 74344

African (AFR) AF: 0.212 AC: 8791 AN: 41450

American (AMR) AF: 0.116 AC: 1771 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0407 AC: 141 AN: 3466

East Asian (EAS) AF: 0.0933 AC: 481 AN: 5158

South Asian (SAS) AF: 0.0475 AC: 229 AN: 4820

European-Finnish (FIN) AF: 0.129 AC: 1370 AN: 10598

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.113 AC: 7704 AN: 67998

Other (OTH) AF: 0.123 AC: 259 AN: 2110

Alfa AF: 0.118 Hom.: 691

Bravo AF: 0.141

Asia WGS AF: 0.0890 AC: 310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	12
DANN	Benign	0.35
PhyloP100		3.5
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9311796; hg19: chr3-61114156;