rs11865665

Positions:

• chr16-1815535-A-G

Variant summary

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

The NM_005326.6(HAGH):​c.747+1358T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0922 in 152,234 control chromosomes in the GnomAD database, including 793 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 0.092 (793 hom., cov: 32)
• Consequence: HAGH NM_005326.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.638

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HAGH	NM_005326.6	c.747+1358T>C		intron_variant		ENST00000397356.8	NP_005317.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HAGH	ENST00000397356.8	c.747+1358T>C		intron_variant		1	NM_005326.6	ENSP00000380514.3

Frequencies

GnomAD3 genomes AF: 0.0919 AC: 13986 AN: 152116 Hom.: 779 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0424

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.119

Gnomad SAS AF: 0.0907

Gnomad FIN AF: 0.0519

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.0717

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

GnomAD4 genome AF: 0.0922 AC: 14031 AN: 152234 Hom.: 793 Cov.: 32 AF XY: 0.0908 AC XY: 6763 AN XY: 74442

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0423

Gnomad4 ASJ AF: 0.0481

Gnomad4 EAS AF: 0.119

Gnomad4 SAS AF: 0.0906

Gnomad4 FIN AF: 0.0519

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0893 Hom.: 83

Bravo AF: 0.0932

Asia WGS AF: 0.135 AC: 470 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.63
DANN	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs11865665; hg19: chr16-1865536;