Genetic Variant CEACAM3:p.Glu133Gly (chr19-41797922-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001815.5(CEACAM3):c.398A>G(p.Glu133Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00333 in 1,609,580 control chromosomes in the GnomAD database, including 149 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 82 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 67 hom. )

Consequence

CEACAM3
NM_001815.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.69

Variant links:

Genes affected

CEACAM3 (HGNC:1815): (CEA cell adhesion molecule 3) This gene encodes a member of the family of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), which are used by several bacterial pathogens to bind and invade host cells. The encoded transmembrane protein directs phagocytosis of several bacterial species that is dependent on the small GTPase Rac. It is thought to serve an important role in controlling human-specific pathogens by the innate immune system. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2013]

CEACAM3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0026091337).

BP6

Variant 19-41797922-A-G is Benign according to our data. Variant chr19-41797922-A-G is described in ClinVar as [Benign]. Clinvar id is 769008.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM3	NM_001815.5 link	c.398A>G	p.Glu133Gly	missense_variant	Exon 2 of 7	ENST00000357396.8	NP_001806.2	P40198-1
CEACAM3	NM_001277163.3 link	c.398A>G	p.Glu133Gly	missense_variant	Exon 2 of 6		NP_001264092.1	P40198-3
CEACAM3	NR_102333.3 link	n.489A>G		non_coding_transcript_exon_variant	Exon 2 of 8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM3	ENST00000357396.8 link	c.398A>G	p.Glu133Gly	missense_variant	Exon 2 of 7	1	NM_001815.5	ENSP00000349971.3		P40198-1

Frequencies

GnomAD3 genomes

AF:

0.0185

AC:

2810

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0648

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00492

AC:

1215

AN:

246944

Hom.:

AF XY:

0.00337

AC XY:

450

AN XY:

133402

show subpopulations

Gnomad AFR exome

AF:

0.0650

Gnomad AMR exome

AF:

0.00376

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000206

Gnomad OTH exome

AF:

0.00183

GnomAD4 exome

AF:

0.00174

AC:

2537

AN:

1457288

Hom.:

Cov.:

AF XY:

0.00152

AC XY:

1100

AN XY:

724948

show subpopulations

Gnomad4 AFR exome

AF:

0.0579

Gnomad4 AMR exome

AF:

0.00425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.00427

GnomAD4 genome

AF:

0.0185

AC:

2822

AN:

152292

Hom.:

Cov.:

AF XY:

0.0176

AC XY:

1312

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.0649

Gnomad4 AMR

AF:

0.00516

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0137

Alfa

AF:

0.00531

Hom.:

Bravo

AF:

0.0219

ESP6500AA

AF:

0.0384

AC:

169

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.00627

AC:

761

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 13, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.59

CADD

Benign

4.2

DANN

Benign

0.97

DEOGEN2

Benign

0.022

T;.;.;T

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.41

T;T;.;T

MetaRNN

Benign

0.0026

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L;L;.

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-4.7

D;.;D;.

REVEL

Benign

0.10

Sift

Benign

0.39

T;.;T;.

Sift4G

Benign

0.40

T;T;T;T

Polyphen

1.0

D;.;.;.

Vest4

0.13

MVP

0.66

MPC

0.53

ClinPred

0.076

GERP RS

-4.7

Varity_R

0.22

gMVP

0.36

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over