rs6925

Positions:

• chr3-58294362-G-A

Variant summary

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

The NM_001320126.2(ABHD6):​c.*597G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 152,666 control chromosomes in the GnomAD database, including 22,342 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 0.52 (22299 hom., cov: 33)
  • Exomes 𝑓: 0.41 (43 hom.)
• Consequence: ABHD6 NM_001320126.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.464

Genes affected

ABHD6 (HGNC:21398): (abhydrolase domain containing 6, acylglycerol lipase) Enables acylglycerol lipase activity. Involved in acylglycerol catabolic process. Predicted to be located in late endosome membrane and lysosomal membrane. Predicted to be integral component of membrane. Predicted to be part of AMPA glutamate receptor complex. Predicted to be active in GABA-ergic synapse; glutamatergic synapse; and mitochondrion. Predicted to be integral component of postsynaptic membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ABHD6	NM_001320126.2	c.*597G>A		3_prime_UTR_variant	10/10	ENST00000478253.6	NP_001307055.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ABHD6	ENST00000478253.6	c.*597G>A		3_prime_UTR_variant	10/10	2	NM_001320126.2	ENSP00000420315	P1
ABHD6	ENST00000295962.8	c.*597G>A		3_prime_UTR_variant	9/9	1		ENSP00000295962	P1
ABHD6	ENST00000480457.1			upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79364 AN: 152000 Hom.: 22272 Cov.: 33

Gnomad AFR AF: 0.734

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.215

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.458

Gnomad OTH AF: 0.480

GnomAD4 exome AF: 0.411 AC: 225 AN: 548 Hom.: 43 Cov.: 0 AF XY: 0.398 AC XY: 128 AN XY: 322

Gnomad4 AFR exome AF: 1.00

Gnomad4 AMR exome AF: 0.250

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.411

Gnomad4 NFE exome AF: 0.422

Gnomad4 OTH exome AF: 0.167

GnomAD4 genome AF: 0.522 AC: 79441 AN: 152118 Hom.: 22299 Cov.: 33 AF XY: 0.518 AC XY: 38540 AN XY: 74364

Gnomad4 AFR AF: 0.734

Gnomad4 AMR AF: 0.442

Gnomad4 ASJ AF: 0.450

Gnomad4 EAS AF: 0.215

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.458

Gnomad4 OTH AF: 0.476

Alfa AF: 0.499 Hom.: 4660

Bravo AF: 0.531

Asia WGS AF: 0.327 AC: 1138 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.1
DANN	Benign	0.45
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6925; hg19: chr3-58280089;