rs201879239

Variant names:

• chr16-55816931-G-A
• rs201879239
• NM_001025195.2:c.938C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-55816931-G-A
• chr16-55816931-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001025195.2(CES1):​c.938C>T​(p.Pro313Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,584 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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: 34)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CES1 NM_001025195.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.51

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25364378).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2	c.938C>T	p.Pro313Leu	missense_variant	Exon 8 of 14	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.935C>T	p.Pro312Leu	missense_variant	Exon 8 of 14		NP_001020365.1
CES1	NM_001266.5	c.935C>T	p.Pro312Leu	missense_variant	Exon 8 of 14		NP_001257.4
CES1	XM_005255774.3	c.938C>T	p.Pro313Leu	missense_variant	Exon 8 of 14		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.938C>T	p.Pro313Leu	missense_variant	Exon 8 of 14	1	NM_001025195.2	ENSP00000353720.4
CES1	ENST00000361503.8	c.935C>T	p.Pro312Leu	missense_variant	Exon 8 of 14	1		ENSP00000355193.4
CES1	ENST00000422046.6	c.935C>T	p.Pro312Leu	missense_variant	Exon 8 of 14	1		ENSP00000390492.2
CES1	ENST00000569260.1	n.77C>T		non_coding_transcript_exon_variant	Exon 2 of 6	5		ENSP00000456865.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461584 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727100

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

Alfa AF: 0.0000434 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.37	.;.;T
Eigen	Benign	-0.097
Eigen_PC	Benign	-0.042
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.59	T;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.79	.;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Pathogenic	-4.9	D;D;D
REVEL	Benign	0.12
Sift	Uncertain	0.0020	D;D;D
Sift4G	Uncertain	0.010	D;D;D
Polyphen		0.48	P;.;P
Vest4		0.29
MutPred		0.49		.;Loss of disorder (P = 0.0682);Loss of disorder (P = 0.0682);
MVP		0.37
MPC		0.11
ClinPred		0.70	D
GERP RS		4.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.54
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs201879239; hg19: chr16-55850843; COSMIC: COSV62089569; COSMIC: COSV62089569;