16-55811002-C-G

Variant names:

• chr16-55811002-C-G
• rs747321428
• NM_001025195.2:c.1095G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001025195.2(CES1):​c.1095G>C​(p.Met365Ile) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CES1 NM_001025195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.77
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.16508341).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001025195.2. 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
	CES1	NM_001025195.2	MANE Select	c.1095G>C	p.Met365Ile	missense	Exon 10 of 14	NP_001020366.1	P23141-2
	CES1	NM_001025194.2		c.1092G>C	p.Met364Ile	missense	Exon 10 of 14	NP_001020365.1	P23141-1
	CES1	NM_001266.5		c.1089G>C	p.Met363Ile	missense	Exon 10 of 14	NP_001257.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	ENST00000360526.8	TSL:1 MANE Select	c.1095G>C	p.Met365Ile	missense	Exon 10 of 14	ENSP00000353720.4	P23141-2
	CES1	ENST00000361503.8	TSL:1	c.1092G>C	p.Met364Ile	missense	Exon 10 of 14	ENSP00000355193.4	P23141-1
	CES1	ENST00000422046.6	TSL:1	c.1089G>C	p.Met363Ile	missense	Exon 10 of 14	ENSP00000390492.2	P23141-3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 122124 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 246188 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

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 Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 1454554 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 723922

African (AFR) AF: 0.00 AC: 0 AN: 33182

American (AMR) AF: 0.00 AC: 0 AN: 44606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39654

South Asian (SAS) AF: 0.00 AC: 0 AN: 85928

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53360

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1105860

Other (OTH) AF: 0.00 AC: 0 AN: 60168

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 122124 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 58400

African (AFR) AF: 0.00 AC: 0 AN: 31074

American (AMR) AF: 0.00 AC: 0 AN: 11188

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3034

East Asian (EAS) AF: 0.00 AC: 0 AN: 4962

South Asian (SAS) AF: 0.00 AC: 0 AN: 4114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7434

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 274

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 57670

Other (OTH) AF: 0.00 AC: 0 AN: 1560

ExAC AF: 0.000173 AC: 21

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	15
DANN	Benign	0.48
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.20	T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.91	L
PhyloP100		3.8
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.059
Sift	Benign	0.36	T
Sift4G	Benign	0.34	T
Polyphen		0.0020	B
Vest4		0.41
MutPred		0.39		Gain of catalytic residue at M364 (P = 0.037)
MVP		0.38
MPC		0.029
ClinPred		0.58	D
GERP RS		3.6
PromoterAI		-0.020	Neutral
Varity_R		0.45
gMVP		0.39

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: rs747321428; hg19: chr16-55844914;