16-55853372-G-T

Variant names:

• chr16-55853372-G-T
• rs1819829
• NM_001143685.2:c.1126-344C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001143685.2(CES5A):​c.1126-344C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.705 in 152,088 control chromosomes in the GnomAD database, including 37,871 homozygotes. 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 0.70 (37871 hom., cov: 33)
• Consequence: CES5A NM_001143685.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.231
• Publications: 3 publications found

Genes affected

CES5A (HGNC:26459): (carboxylesterase 5A) 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 also participate in fatty acyl and cholesterol ester metabolism, and may play a role in the blood-brain barrier system. This gene, also called CES5, is predominantly expressed in peripheral tissues, including brain, kidney, lung and testis. It encodes a secreted enzyme. Because of high levels in the urine of male domestic cats, this enzyme is also called cauxin (carboxylesterase-like urinary excreted protein). The enzyme functions in regulating the production of a pheromone precursor and may contribute to lipid and cholesterol transfer processes within male reproductive fluids. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001143685.2. 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
	CES5A	NM_001143685.2	MANE Select	c.1126-344C>A		intron	N/A	NP_001137157.1
	CES5A	NM_001190158.1		c.1213-344C>A		intron	N/A	NP_001177087.1
	CES5A	NM_145024.3		c.1126-344C>A		intron	N/A	NP_659461.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES5A	ENST00000290567.14	TSL:1 MANE Select	c.1126-344C>A		intron	N/A	ENSP00000290567.9
	CES5A	ENST00000319165.13	TSL:1	c.1126-344C>A		intron	N/A	ENSP00000324271.9
	CES5A	ENST00000521992.5	TSL:2	c.1213-344C>A		intron	N/A	ENSP00000428864.1

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107064 AN: 151970 Hom.: 37845 Cov.: 33

Gnomad AFR AF: 0.637

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.764

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.615

Gnomad FIN AF: 0.742

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.709

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

GnomAD4 genome AF: 0.705 AC: 107151 AN: 152088 Hom.: 37871 Cov.: 33 AF XY: 0.705 AC XY: 52426 AN XY: 74362

African (AFR) AF: 0.637 AC: 26423 AN: 41466

American (AMR) AF: 0.766 AC: 11709 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 2648 AN: 3468

East Asian (EAS) AF: 0.773 AC: 3986 AN: 5158

South Asian (SAS) AF: 0.616 AC: 2969 AN: 4822

European-Finnish (FIN) AF: 0.742 AC: 7866 AN: 10598

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49185 AN: 67976

Other (OTH) AF: 0.708 AC: 1493 AN: 2108

Alfa AF: 0.724 Hom.: 6762

Bravo AF: 0.707

Asia WGS AF: 0.686 AC: 2385 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.67
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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: rs1819829; hg19: chr16-55887284;