rs780773594

Variant names:

• chr16-67003266-A-C
• rs780773594
• NM_001364782.1:c.806A>C

Your query was ambiguous. Multiple possible variants found:

• chr16-67003266-A-C
• chr16-67003266-A-G
• chr16-67003266-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364782.1(CES4A):​c.806A>C​(p.His269Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H269R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CES4A NM_001364782.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.403
• Publications: 0 publications found

Genes affected

CES4A (HGNC:26741): (carboxylesterase 4A) 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 CES6, encodes a secreted enzyme, and may play a role in the detoxification of drugs and xenobiotics in neural and other tissues of the body and in the cerebrospinal fluid. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature and/or biological validity of some variants have not been determined. [provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11505553).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364782.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES4A	NM_001364782.1	MANE Select	c.806A>C	p.His269Pro	missense	Exon 7 of 14	NP_001351711.1	Q5XG92-1
	CES4A	NM_173815.7		c.806A>C	p.His269Pro	missense	Exon 7 of 12	NP_776176.5
	CES4A	NM_001190201.2		c.512A>C	p.His171Pro	missense	Exon 5 of 12	NP_001177130.1	Q5XG92-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CES4A	ENST00000648724.3	MANE Select	c.806A>C	p.His269Pro	missense	Exon 7 of 14	ENSP00000497868.2	Q5XG92-1
	CES4A	ENST00000540579.6	TSL:1	c.512A>C	p.His171Pro	missense	Exon 5 of 12	ENSP00000441907.1	Q5XG92-6
	CES4A	ENST00000538199.5	TSL:1	c.695A>C	p.His232Pro	missense	Exon 6 of 11	ENSP00000441103.1	A0A0C4DGH1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.057	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	4.5
DANN	Benign	0.62
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.27	T
M_CAP	Benign	0.0098	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.74	N
PhyloP100		-0.40
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.17
Sift	Benign	0.26	T
Sift4G	Benign	0.19	T
Polyphen		0.010	B
Vest4		0.30
MutPred		0.40		Loss of MoRF binding (P = 0.0906)
MVP		0.27
MPC		0.73
ClinPred		0.060	T
GERP RS		-4.4
gMVP		0.89

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: rs780773594; hg19: chr16-67037169;