Genetic Variant ABHD6:c.*597G>A (chr3-58294362-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.464

Publications

12 publications found

Variant links:

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]

ABHD6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320126.2. 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
	ABHD6	NM_001320126.2	MANE Select	c.*597G>A		3_prime_UTR	Exon 10 of 10	NP_001307055.1
	ABHD6	NM_020676.7		c.*597G>A		3_prime_UTR	Exon 9 of 9	NP_065727.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
ABHD6	ENST00000478253.6	TSL:2 MANE Select	c.*597G>A	3_prime_UTR	Exon 10 of 10	ENSP00000420315.1
ABHD6	ENST00000295962.8	TSL:1	c.*597G>A	3_prime_UTR	Exon 9 of 9	ENSP00000295962.4
ABHD6	ENST00000480457.1	TSL:3	n.-1G>A	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.522

AC:

79364

AN:

152000

Hom.:

22272

Cov.:

show subpopulations

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.:

Cov.:

AF XY:

0.398

AC XY:

128

AN XY:

322

show subpopulations

African (AFR)

AF:

1.00

AC:

AN:

American (AMR)

AF:

0.250

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.500

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.411

AC:

176

AN:

428

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.422

AC:

AN:

102

Other (OTH)

AF:

0.167

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.522

AC:

79441

AN:

152118

Hom.:

22299

Cov.:

AF XY:

0.518

AC XY:

38540

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.734

AC:

30451

AN:

41502

American (AMR)

AF:

0.442

AC:

6752

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1560

AN:

3464

East Asian (EAS)

AF:

0.215

AC:

1113

AN:

5178

South Asian (SAS)

AF:

0.372

AC:

1799

AN:

4830

European-Finnish (FIN)

AF:

0.482

AC:

5088

AN:

10566

Middle Eastern (MID)

AF:

0.439

AC:

129

AN:

294

European-Non Finnish (NFE)

AF:

0.458

AC:

31149

AN:

67988

Other (OTH)

AF:

0.476

AC:

1006

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1829

3658

5487

7316

9145

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

670

1340

2010

2680

3350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.1

(source)

DANN

Benign

0.45

PhyloP100

0.46

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over