NM_001025195.2:c.52+629T>A

Variant names:

• chr16-55832375-A-T
• rs7188256
• NM_001025195.2:c.52+629T>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001025195.2(CES1):​c.52+629T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.0000068 (0 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: CES1 NM_001025195.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.284
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	NM_001025195.2	MANE Select	c.52+629T>A		intron	N/A	NP_001020366.1
	CES1	NM_001025194.2		c.52+629T>A		intron	N/A	NP_001020365.1
	CES1	NM_001266.5		c.52+629T>A		intron	N/A	NP_001257.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES1	ENST00000360526.8	TSL:1 MANE Select	c.52+629T>A		intron	N/A	ENSP00000353720.4
	CES1	ENST00000361503.8	TSL:1	c.52+629T>A		intron	N/A	ENSP00000355193.4
	CES1	ENST00000422046.6	TSL:1	c.52+629T>A		intron	N/A	ENSP00000390492.2

Frequencies

GnomAD3 genomes AF: 0.00000677 AC: 1 AN: 147774 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000669

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000677 AC: 1 AN: 147774 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 72190

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

African (AFR) AF: 0.00 AC: 0 AN: 39276

American (AMR) AF: 0.0000669 AC: 1 AN: 14944

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3362

East Asian (EAS) AF: 0.00 AC: 0 AN: 5108

South Asian (SAS) AF: 0.00 AC: 0 AN: 4722

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 300

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66910

Other (OTH) AF: 0.00 AC: 0 AN: 2026

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.64
PhyloP100		-0.28

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: rs7188256; hg19: chr16-55866287;