19-42522070-G-T

Position:

chr19-42522070-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_001712.5(CEACAM1):c.557C>A(p.Pro186Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 1,614,162 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00082 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 1 hom. )

Consequence

CEACAM1
NM_001712.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.821

Variant links:

Genes affected

CEACAM1 (HGNC:1814): (CEA cell adhesion molecule 1) This gene encodes a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin superfamily. Two subgroups of the CEA family, the CEA cell adhesion molecules and the pregnancy-specific glycoproteins, are located within a 1.2 Mb cluster on the long arm of chromosome 19. Eleven pseudogenes of the CEA cell adhesion molecule subgroup are also found in the cluster. The encoded protein was originally described in bile ducts of liver as biliary glycoprotein. Subsequently, it was found to be a cell-cell adhesion molecule detected on leukocytes, epithelia, and endothelia. The encoded protein mediates cell adhesion via homophilic as well as heterophilic binding to other proteins of the subgroup. Multiple cellular activities have been attributed to the encoded protein, including roles in the differentiation and arrangement of tissue three-dimensional structure, angiogenesis, apoptosis, tumor suppression, metastasis, and the modulation of innate and adaptive immune responses. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature of all variants has not been defined. [provided by RefSeq, May 2010]

CEACAM1 links:

CEACAM1 (HGNC:):

CEACAM1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM1	NM_001712.5 linkuse as main transcript	c.557C>A	p.Pro186Gln	missense_variant	3/9	ENST00000161559.11	NP_001703.2	P13688-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM1	ENST00000161559.11 linkuse as main transcript	c.557C>A	p.Pro186Gln	missense_variant	3/9	1	NM_001712.5	ENSP00000161559.6		P13688-1

Frequencies

GnomAD3 genomes

AF:

0.000828

AC:

126

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00141

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000744

AC:

187

AN:

251492

Hom.:

AF XY:

0.000780

AC XY:

106

AN XY:

135920

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00141

Gnomad OTH exome

AF:

0.00114

GnomAD4 exome

AF:

0.00141

AC:

2059

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00131

AC XY:

953

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.000425

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.00175

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.000821

AC:

125

AN:

152278

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000588

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000540

Hom.:

Bravo

AF:

0.000948

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00182

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000659

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00115

EpiControl

AF:

0.00124

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 29, 2024

The c.557C>A (p.P186Q) alteration is located in exon 3 (coding exon 3) of the CEACAM1 gene. This alteration results from a C to A substitution at nucleotide position 557, causing the proline (P) at amino acid position 186 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.5

DANN

Benign

0.88

DEOGEN2

Benign

0.34

.;T;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.014

LIST_S2

Benign

0.51

T;T;T;T;T;T

M_CAP

Benign

0.0026

MetaRNN

Benign

0.013

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

L;L;L;L;L;L

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Pathogenic

-5.1

D;D;D;D;D;.

REVEL

Benign

0.033

Sift

Benign

0.23

T;T;T;T;T;.

Sift4G

Benign

0.19

T;T;T;T;T;T

Polyphen

0.92

P;P;P;P;P;.

Vest4

0.26

MVP

0.17

MPC

0.22

ClinPred

0.11

GERP RS

-5.4

Varity_R

0.097

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.43

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.43

Position offset: -1

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