4-127982986-C-T

Variant names:

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

Variant summary

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

The NM_001366038.3(ABHD18):​c.-771C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 1,565,956 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: ABHD18 NM_001366038.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001366038.3. 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>T	p.Arg11Trp	missense	Exon 2 of 13	NP_001345380.1	A0A2R8YEZ0
	ABHD18	NM_001366038.3		c.-771C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 14	NP_001352967.1
	ABHD18	NM_001319305.3		c.-160C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 13	NP_001306234.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ABHD18	ENST00000645843.2	MANE Select	c.31C>T	p.Arg11Trp	missense	Exon 2 of 13	ENSP00000496010.1	A0A2R8YEZ0
	ABHD18	ENST00000444616.5	TSL:5	c.31C>T	p.Arg11Trp	missense	Exon 2 of 11	ENSP00000397229.1	Q0P651-1
	ABHD18	ENST00000388795.10	TSL:5	n.31C>T		non_coding_transcript_exon	Exon 2 of 13	ENSP00000373447.6	B7WP89

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 152056 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000221 AC: 4 AN: 180710 AF XY: 0.0000105

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000149

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000269

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000170 AC: 24 AN: 1413900 Hom.: 0 Cov.: 30 AF XY: 0.0000186 AC XY: 13 AN XY: 698658

African (AFR) AF: 0.0000309 AC: 1 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: 0.0000266 AC: 1 AN: 37622

South Asian (SAS) AF: 0.0000125 AC: 1 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: 0.0000166 AC: 18 AN: 1085954

Other (OTH) AF: 0.0000512 AC: 3 AN: 58642

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152056 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74254

African (AFR) AF: 0.00 AC: 0 AN: 41408

American (AMR) AF: 0.0000656 AC: 1 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000264

ExAC AF: 0.0000254 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.38	D
BayesDel_noAF	Pathogenic	0.31
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.76	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.64	D
MetaSVM	Uncertain	-0.21	T
PhyloP100		1.6
PROVEAN	Pathogenic	-6.4	D
REVEL	Pathogenic	0.79
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.92
MutPred		0.70		Gain of catalytic residue at L9 (P = 0.0084)
MVP		0.64
MPC		0.60
ClinPred		0.94	D
GERP RS		5.4
Varity_R		0.61
gMVP		0.94
Mutation Taster		=51/49	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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; COSMIC: COSV66293804;