rs3764349

Positions:

• chr16-1795604-C-T

Variant summary

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

The 16-1795604-C-T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,208 control chromosomes in the GnomAD database, including 4,399 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 0.19 (4399 hom., cov: 32)
  • Exomes 𝑓: 0.071 (0 hom.)
• Consequence: HAGH ENST00000564445.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03

Genes affected

HAGH (HGNC:4805): (hydroxyacylglutathione hydrolase) The enzyme encoded by this gene is classified as a thiolesterase and is responsible for the hydrolysis of S-lactoyl-glutathione to reduced glutathione and D-lactate. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.413 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAGH	ENST00000564445.5			downstream_gene_variant		3		ENSP00000455355

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29070 AN: 151978 Hom.: 4385 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.0637

Gnomad AMR AF: 0.105

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.159

Gnomad SAS AF: 0.248

Gnomad FIN AF: 0.0661

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.169

GnomAD4 exome AF: 0.0714 AC: 8 AN: 112 Hom.: 0 Cov.: 0 AF XY: 0.0541 AC XY: 4 AN XY: 74

Gnomad4 AMR exome AF: 0.125

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0581

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.191 AC: 29118 AN: 152096 Hom.: 4399 Cov.: 32 AF XY: 0.188 AC XY: 14007 AN XY: 74376

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.159

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.0661

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.176

Alfa AF: 0.153 Hom.: 310

Bravo AF: 0.200

Asia WGS AF: 0.232 AC: 806 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	5.8
DANN	Benign	0.32

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3764349; hg19: chr16-1845605;