ENST00000506207.2:n.236+4013T>C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HINT1	ENST00000506207.2	n.236+4013T>C		intron_variant	Intron 2 of 3	5

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

Gnomad4 AFR AF: 0.120

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.540

Gnomad4 EAS AF: 0.422

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.508

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.495

Alfa AF: 0.555 Hom.: 6220

Bravo AF: 0.449

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2526303; hg19: chr5-130503286;