chr16-55823599-C-G

Variant names:

• chr16-55823599-C-G
• rs372957576
• NM_001025195.2:c.490G>C

Variant summary

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

The NM_001025195.2(CES1):​c.490G>C​(p.Val164Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 39)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 NM_001025195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.54

Genes affected

CES1 (HGNC:1863): (carboxylesterase 1) 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 may participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This enzyme is the major liver enzyme and functions in liver drug clearance. Mutations of this gene cause carboxylesterase 1 deficiency. Three transcript variants encoding three different isoforms have been found for this gene. [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, 0.861

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2	c.490G>C	p.Val164Leu	missense_variant	Exon 4 of 14	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.487G>C	p.Val163Leu	missense_variant	Exon 4 of 14		NP_001020365.1
CES1	NM_001266.5	c.487G>C	p.Val163Leu	missense_variant	Exon 4 of 14		NP_001257.4
CES1	XM_005255774.3	c.490G>C	p.Val164Leu	missense_variant	Exon 4 of 14		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.490G>C	p.Val164Leu	missense_variant	Exon 4 of 14	1	NM_001025195.2	ENSP00000353720.4

Frequencies

GnomAD3 genomes Cov.: 39

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1461670 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727150

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 39

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.48	.;.;T
Eigen	Uncertain	0.22
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.89	D;D;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.86	D;D;D
MetaSVM	Uncertain	0.12	D
MutationAssessor	Uncertain	2.6	.;M;M
PrimateAI	Benign	0.45	T
PROVEAN	Uncertain	-2.9	D;D;D
REVEL	Pathogenic	0.65
Sift	Benign	0.043	D;D;D
Sift4G	Uncertain	0.026	D;D;D
Polyphen		0.81	P;.;P
Vest4		0.69
MutPred		0.86		.;Gain of helix (P = 0.132);Gain of helix (P = 0.132);
MVP		0.30
MPC		0.057
ClinPred		0.90	D
GERP RS		4.0
Varity_R		0.76
gMVP		0.57

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

LitVar

Other links and lift over

dbSNP: rs372957576; hg19: chr16-55857511;