rs4815412

Variant names:

• chr20-25369689-G-A
• rs4815412
• NM_001042472.3:c.191+20824C>T

Variant summary

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

The NM_001042472.3(ABHD12):​c.191+20824C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 152,050 control chromosomes in the GnomAD database, including 22,830 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 0.54 (22830 hom., cov: 32)
• Consequence: ABHD12 NM_001042472.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• Publications: 13 publications found

Genes affected

ABHD12 (HGNC:15868): (abhydrolase domain containing 12, lysophospholipase) This gene encodes an enzyme that catalyzes the hydrolysis of 2-arachidonoyl glycerol (2-AG), the main endocannabinoid lipid transmitter that acts on cannabinoid receptors, CB1 and CB2. The endocannabinoid system is involved in a wide range of physiological processes, including neurotransmission, mood, appetite, pain appreciation, addiction behavior, and inflammation. Mutations in this gene are associated with the neurodegenerative disease, PHARC (polyneuropathy, hearing loss, ataxia, retinitis pigmentosa, and cataract), resulting from an inborn error of endocannabinoid metabolism. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene.[provided by RefSeq, Jan 2011]

ABHD12 Gene-Disease associations (from GenCC):

• PHARC syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, Orphanet, ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042472.3. 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
	ABHD12	NM_001042472.3	MANE Select	c.191+20824C>T		intron	N/A	NP_001035937.1
	ABHD12	NM_015600.5		c.191+20824C>T		intron	N/A	NP_056415.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD12	ENST00000339157.10	TSL:2 MANE Select	c.191+20824C>T		intron	N/A	ENSP00000341408.5
	ABHD12	ENST00000376542.8	TSL:1	c.191+20824C>T		intron	N/A	ENSP00000365725.3
	ABHD12	ENST00000673121.1		c.-281+20237C>T		intron	N/A	ENSP00000499839.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82169 AN: 151932 Hom.: 22804 Cov.: 32

Gnomad AFR AF: 0.538

Gnomad AMI AF: 0.486

Gnomad AMR AF: 0.610

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.0827

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.549

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.541 AC: 82244 AN: 152050 Hom.: 22830 Cov.: 32 AF XY: 0.540 AC XY: 40143 AN XY: 74334

African (AFR) AF: 0.538 AC: 22286 AN: 41462

American (AMR) AF: 0.611 AC: 9325 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2359 AN: 3470

East Asian (EAS) AF: 0.0823 AC: 426 AN: 5178

South Asian (SAS) AF: 0.525 AC: 2528 AN: 4818

European-Finnish (FIN) AF: 0.549 AC: 5796 AN: 10566

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.555 AC: 37728 AN: 67976

Other (OTH) AF: 0.565 AC: 1189 AN: 2106

Alfa AF: 0.560 Hom.: 4211

Bravo AF: 0.544

Asia WGS AF: 0.319 AC: 1111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.60
PhyloP100		0.64
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4815412; hg19: chr20-25350325;