rs2244613

Variant names:

• chr16-55810697-G-A
• rs2244613
• NM_001025195.2:c.1171-33C>T

Your query was ambiguous. Multiple possible variants found:

• chr16-55810697-G-A
• chr16-55810697-G-C
• chr16-55810697-G-T

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.1171-33C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,822 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: 34)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CES1 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 95 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=-0.89).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CES1	NM_001025195.2	c.1171-33C>T		intron_variant	Intron 10 of 13	ENST00000360526.8	NP_001020366.1
CES1	NM_001025194.2	c.1168-33C>T		intron_variant	Intron 10 of 13		NP_001020365.1
CES1	NM_001266.5	c.1165-33C>T		intron_variant	Intron 10 of 13		NP_001257.4
CES1	XM_005255774.3	c.1168-33C>T		intron_variant	Intron 10 of 13		XP_005255831.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CES1	ENST00000360526.8	c.1171-33C>T		intron_variant	Intron 10 of 13	1	NM_001025195.2	ENSP00000353720.4

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD2 exomes AF: 0.00000801 AC: 2 AN: 249766 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460822 Hom.: 0 Cov.: 48 AF XY: 0.00000138 AC XY: 1 AN XY: 726746

⚠️ 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: 33472

American (AMR) AF: 0.0000224 AC: 1 AN: 44692

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111128

Other (OTH) AF: 0.0000166 AC: 1 AN: 60342

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000145500), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 157154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.32
DANN	Benign	0.62
PhyloP100		-1.6
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2244613; hg19: chr16-55844609;