rs539063507

Variant names:

• chr16-66988822-C-G
• NM_001364782.1:c.50C>G

Your query was ambiguous. Multiple possible variants found:

• chr16-66988822-C-G
• chr16-66988822-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001364782.1(CES4A):​c.50C>G​(p.Thr17Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,414,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 13/20 in silico tools predict 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: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CES4A NM_001364782.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299

Genes affected

CES4A (HGNC:26741): (carboxylesterase 4A) This gene encodes a member of the carboxylesterase large family. The family members are responsible for the hydrolysis or transesterification of various xenobiotics, such as cocaine and heroin, and endogenous substrates with ester, thioester, or amide bonds. They also participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This gene, also called CES6, encodes a secreted enzyme, and may play a role in the detoxification of drugs and xenobiotics in neural and other tissues of the body and in the cerebrospinal fluid. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature and/or biological validity of some variants have not been determined. [provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES4A	NM_001364782.1	c.50C>G	p.Thr17Arg	missense_variant	Exon 1 of 14	ENST00000648724.3	NP_001351711.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES4A	ENST00000648724.3	c.50C>G	p.Thr17Arg	missense_variant	Exon 1 of 14		NM_001364782.1	ENSP00000497868.2
CES4A	ENST00000540947.6	c.50C>G	p.Thr17Arg	missense_variant	Exon 1 of 12	2		ENSP00000444052.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000141 AC: 2 AN: 1414442 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 699436

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000184

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	16
DANN	Uncertain	0.98
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.43
FATHMM_MKL	Benign	0.029	N
LIST_S2	Benign	0.36	T;.
M_CAP	Benign	0.013	T
MetaRNN	Pathogenic	0.87	D;D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-2.0	N;.
REVEL	Uncertain	0.33
Sift	Benign	0.40	T;.
Sift4G	Benign	0.36	T;.
Vest4		0.41
MutPred		0.93		.;Gain of MoRF binding (P = 0.0175);
MVP		0.70
MPC		0.57
ClinPred		0.30	T
GERP RS		2.5
gMVP		0.33

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-67022725;