16-1813980-C-G

Variant names:

• chr16-1813980-C-G
• rs11859266
• NM_005326.6:c.747+2913G>C

Variant summary

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

The NM_005326.6(HAGH):​c.747+2913G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0933 in 152,218 control chromosomes in the GnomAD database, including 818 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 0.093 (818 hom., cov: 32)
• Consequence: HAGH NM_005326.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005326.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAGH	NM_005326.6	MANE Select	c.747+2913G>C		intron	N/A	NP_005317.2
	HAGH	NM_001363912.1		c.747+2913G>C		intron	N/A	NP_001350841.1
	HAGH	NM_001040427.2		c.603+2913G>C		intron	N/A	NP_001035517.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HAGH	ENST00000397356.8	TSL:1 MANE Select	c.747+2913G>C		intron	N/A	ENSP00000380514.3
	HAGH	ENST00000945501.1		c.786+2913G>C		intron	N/A	ENSP00000615560.1
	HAGH	ENST00000851988.1		c.747+2913G>C		intron	N/A	ENSP00000522047.1

Frequencies

GnomAD3 genomes AF: 0.0931 AC: 14161 AN: 152100 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0285

Gnomad AMR AF: 0.0428

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.120

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.0516

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.0722

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

GnomAD4 genome AF: 0.0933 AC: 14206 AN: 152218 Hom.: 818 Cov.: 32 AF XY: 0.0920 AC XY: 6847 AN XY: 74432

African (AFR) AF: 0.163 AC: 6757 AN: 41518

American (AMR) AF: 0.0426 AC: 652 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 167 AN: 3472

East Asian (EAS) AF: 0.119 AC: 617 AN: 5172

South Asian (SAS) AF: 0.0909 AC: 439 AN: 4828

European-Finnish (FIN) AF: 0.0516 AC: 548 AN: 10614

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0708 AC: 4813 AN: 68002

Other (OTH) AF: 0.0824 AC: 174 AN: 2112

Alfa AF: 0.0246 Hom.: 14

Bravo AF: 0.0944

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.85
DANN	Benign	0.25
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs11859266; hg19: chr16-1863981;