4-127982986-C-A

Variant names:

• chr4-127982986-C-A
• rs750671699
• NM_001358451.3:c.31C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4 BP7

The NM_001358451.3(ABHD18):​c.31C>A​(p.Arg11Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,900 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: ABHD18 NM_001358451.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 3 publications found

Genes affected

ABHD18 (HGNC:26111): (abhydrolase domain containing 18) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.16).
• BP7: Synonymous conserved (PhyloP=1.57 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358451.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD18	NM_001358451.3	MANE Select	c.31C>A	p.Arg11Arg	synonymous	Exon 2 of 13	NP_001345380.1	A0A2R8YEZ0
	ABHD18	NM_001358454.3		c.31C>A	p.Arg11Arg	synonymous	Exon 2 of 14	NP_001345383.1
	ABHD18	NM_001366043.1		c.31C>A	p.Arg11Arg	synonymous	Exon 2 of 12	NP_001352972.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD18	ENST00000645843.2	MANE Select	c.31C>A	p.Arg11Arg	synonymous	Exon 2 of 13	ENSP00000496010.1	A0A2R8YEZ0
	ABHD18	ENST00000444616.5	TSL:5	c.31C>A	p.Arg11Arg	synonymous	Exon 2 of 11	ENSP00000397229.1	Q0P651-1
	ABHD18	ENST00000388795.10	TSL:5	n.31C>A		non_coding_transcript_exon	Exon 2 of 13	ENSP00000373447.6	B7WP89

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000553 AC: 1 AN: 180710 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000376

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.07e-7 AC: 1 AN: 1413900 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 698658

African (AFR) AF: 0.00 AC: 0 AN: 32386

American (AMR) AF: 0.00 AC: 0 AN: 37532

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25326

East Asian (EAS) AF: 0.00 AC: 0 AN: 37622

South Asian (SAS) AF: 0.00 AC: 0 AN: 80102

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50634

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5702

European-Non Finnish (NFE) AF: 9.21e-7 AC: 1 AN: 1085954

Other (OTH) AF: 0.00 AC: 0 AN: 58642

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.16
CADD	Benign	9.9
DANN	Benign	0.71
PhyloP100		1.6

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: rs750671699; hg19: chr4-128904141;