5-131170068-C-A

Variant names:

• chr5-131170068-C-A
• rs7735116
• ENST00000506207.2:n.236+1538G>T

Variant summary

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

The ENST00000506207.2(HINT1):​n.236+1538G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.181 in 152,066 control chromosomes in the GnomAD database, including 6,301 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 0.18 (6301 hom., cov: 32)
• Consequence: HINT1 ENST00000506207.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.666
• Publications: 4 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=-0.7).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.533 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+1538G>T		intron_variant	Intron 2 of 3	5

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27445 AN: 151948 Hom.: 6285 Cov.: 32

Gnomad AFR AF: 0.539

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0923

Gnomad ASJ AF: 0.111

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.0489

Gnomad FIN AF: 0.00916

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.0391

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.181 AC: 27498 AN: 152066 Hom.: 6301 Cov.: 32 AF XY: 0.175 AC XY: 13002 AN XY: 74336

African (AFR) AF: 0.539 AC: 22328 AN: 41432

American (AMR) AF: 0.0921 AC: 1407 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 386 AN: 3466

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5176

South Asian (SAS) AF: 0.0489 AC: 236 AN: 4824

European-Finnish (FIN) AF: 0.00916 AC: 97 AN: 10584

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.0391 AC: 2659 AN: 67996

Other (OTH) AF: 0.157 AC: 330 AN: 2106

Alfa AF: 0.0709 Hom.: 3106

Bravo AF: 0.204

Asia WGS AF: 0.0640 AC: 225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	14
DANN	Benign	0.77
PhyloP100		0.67

Splicing

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

Other links and lift over

dbSNP: rs7735116; hg19: chr5-130505761;