16-55833094-T-G

Variant names:

• chr16-55833094-T-G
• rs12149371
• NM_001025195.2:c.-39A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001025195.2(CES1):​c.-39A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000229 in 1,308,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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: 0.0000023 (0 hom.)
• Consequence: CES1 NM_001025195.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.59
• 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2	c.-39A>C		5_prime_UTR_variant	Exon 1 of 14	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.-39A>C		5_prime_UTR_variant	Exon 1 of 14		NP_001020365.1
CES1	NM_001266.5	c.-39A>C		5_prime_UTR_variant	Exon 1 of 14		NP_001257.4
CES1	XM_005255774.3	c.-39A>C		5_prime_UTR_variant	Exon 1 of 14		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.-39A>C		5_prime_UTR_variant	Exon 1 of 14	1	NM_001025195.2	ENSP00000353720.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000229 AC: 3 AN: 1308496 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 653202

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30512

American (AMR) AF: 0.00 AC: 0 AN: 42890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24380

East Asian (EAS) AF: 0.00 AC: 0 AN: 34232

South Asian (SAS) AF: 0.00 AC: 0 AN: 79070

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5056

European-Non Finnish (NFE) AF: 0.00000304 AC: 3 AN: 988336

Other (OTH) AF: 0.00 AC: 0 AN: 54448

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.010
DANN	Benign	0.25
PhyloP100		-4.6
PromoterAI		0.027	Neutral

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: rs12149371; hg19: chr16-55867006;