5-131167593-A-G

Variant names:

• chr5-131167593-A-G
• rs2526303
• ENST00000506207.2:n.236+4013T>C

Variant summary

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

The ENST00000506207.2(HINT1):​n.236+4013T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 152,096 control chromosomes in the GnomAD database, including 19,850 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 0.46 (19850 hom., cov: 32)
• Consequence: HINT1 ENST00000506207.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 10 publications found

Genes affected

HINT1 (HGNC:4912): (histidine triad nucleotide binding protein 1) This gene encodes a protein that hydrolyzes purine nucleotide phosphoramidates substrates, including AMP-morpholidate, AMP-N-alanine methyl ester, AMP-alpha-acetyl lysine methyl ester, and AMP-NH2. The encoded protein interacts with these substrates via a histidine triad motif. This gene is considered a tumor suppressor gene. In addition, mutations in this gene can cause autosomal recessive neuromyotonia and axonal neuropathy. There are several related pseudogenes on chromosome 7. Several transcript variants have been observed. [provided by RefSeq, Dec 2015]

HINT1 Gene-Disease associations (from GenCC):

• Charcot-Marie-Tooth disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Gamstorp-Wohlfart syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000506207.2. 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

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HINT1	ENST00000506207.2	TSL:5	n.236+4013T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70046 AN: 151978 Hom.: 19851 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.540

Gnomad EAS AF: 0.422

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.495

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

GnomAD4 genome AF: 0.461 AC: 70043 AN: 152096 Hom.: 19850 Cov.: 32 AF XY: 0.458 AC XY: 34061 AN XY: 74344

African (AFR) AF: 0.120 AC: 4993 AN: 41520

American (AMR) AF: 0.537 AC: 8206 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.540 AC: 1871 AN: 3468

East Asian (EAS) AF: 0.422 AC: 2175 AN: 5152

South Asian (SAS) AF: 0.544 AC: 2622 AN: 4816

European-Finnish (FIN) AF: 0.508 AC: 5371 AN: 10564

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43038 AN: 67976

Other (OTH) AF: 0.495 AC: 1045 AN: 2112

Alfa AF: 0.560 Hom.: 9865

Bravo AF: 0.449

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.0
DANN	Benign	0.78
PhyloP100		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2526303; hg19: chr5-130503286;