rs12522164

Positions:

• chr5-131214920-G-A
• chr5-131214920-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000702509.1(ENSG00000290020):​n.116+4757G>A variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0985 in 152,264 control chromosomes in the GnomAD database, including 920 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 0.099 (920 hom., cov: 32)
• Consequence: ENST00000702509.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295

Genes affected

(HGNC:):

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=-0.87).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC124901061	XR_007058932.1	n.112-4767C>T		intron_variant, non_coding_transcript_variant
CDC42SE2	XM_047417393.1	c.-797+4757G>A		intron_variant			XP_047273349.1
CDC42SE2	XM_047417396.1	c.-1028+4757G>A		intron_variant			XP_047273352.1
LOC124901061	XR_007058931.1	n.524-4767C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000702509.1	n.116+4757G>A		intron_variant, non_coding_transcript_variant
HINT1	ENST00000506207.2	n.108+9441C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0986 AC: 15001 AN: 152144 Hom.: 918 Cov.: 32

Gnomad AFR AF: 0.0381

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.0435

Gnomad EAS AF: 0.118

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.0970

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

GnomAD4 genome AF: 0.0985 AC: 15000 AN: 152264 Hom.: 920 Cov.: 32 AF XY: 0.101 AC XY: 7480 AN XY: 74426

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.0948

Gnomad4 ASJ AF: 0.0435

Gnomad4 EAS AF: 0.118

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.155

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.0989

Alfa AF: 0.0371 Hom.: 36

Bravo AF: 0.0889

Asia WGS AF: 0.135 AC: 472 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.8
DANN	Benign	0.66

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12522164; hg19: chr5-130550613;