19-42527096-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001712.5(CEACAM1):c.369A>C(p.Gln123His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,582,376 control chromosomes in the GnomAD database, including 3,383 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.096 ( 1838 hom., cov: 32)

Exomes 𝑓: 0.011 ( 1545 hom. )

Consequence

CEACAM1
NM_001712.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.961

Publications

13 publications found

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:

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

LIPE-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.011648744).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM1	NM_001712.5 link	c.369A>C	p.Gln123His	missense_variant	Exon 2 of 9	ENST00000161559.11	NP_001703.2	P13688-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM1	ENST00000161559.11 link	c.369A>C	p.Gln123His	missense_variant	Exon 2 of 9	1	NM_001712.5	ENSP00000161559.6		P13688-1

Frequencies

GnomAD3 genomes

AF:

0.0960

AC:

14550

AN:

151634

Hom.:

1826

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0448

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.0764

GnomAD2 exomes

AF:

0.0284

AC:

6858

AN:

241440

AF XY:

0.0211

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.0204

Gnomad ASJ exome

AF:

0.00719

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.00396

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.0113

AC:

16151

AN:

1430628

Hom.:

1545

Cov.:

AF XY:

0.0100

AC XY:

7147

AN XY:

712180

show subpopulations

African (AFR)

AF:

0.351

AC:

11503

AN:

32800

American (AMR)

AF:

0.0221

AC:

972

AN:

44070

Ashkenazi Jewish (ASJ)

AF:

0.00495

AC:

127

AN:

25646

East Asian (EAS)

AF:

0.000302

AC:

AN:

39700

South Asian (SAS)

AF:

0.00110

AC:

AN:

85750

European-Finnish (FIN)

AF:

0.000649

AC:

AN:

52370

Middle Eastern (MID)

AF:

0.0320

AC:

184

AN:

5750

European-Non Finnish (NFE)

AF:

0.00150

AC:

1626

AN:

1085110

Other (OTH)

AF:

0.0269

AC:

1599

AN:

59432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

721

1443

2164

2886

3607

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

360

720

1080

1440

1800

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0963

AC:

14611

AN:

151748

Hom.:

1838

Cov.:

AF XY:

0.0926

AC XY:

6871

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.331

AC:

13585

AN:

41042

American (AMR)

AF:

0.0447

AC:

683

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3472

East Asian (EAS)

AF:

0.000772

AC:

AN:

5184

South Asian (SAS)

AF:

0.00166

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.0272

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00193

AC:

131

AN:

68014

Other (OTH)

AF:

0.0813

AC:

171

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

494

988

1482

1976

2470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

140

280

420

560

700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0543

Hom.:

389

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.340

AC:

1500

ESP6500EA

AF:

0.00326

AC:

ExAC

AF:

0.0401

AC:

4865

Asia WGS

AF:

0.0530

AC:

183

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.39

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.52

CADD

Benign

6.5

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.13

.;T;.;.;.;.;.;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.032

LIST_S2

Benign

0.024

T;T;T;T;T;T;T;T

MetaRNN

Benign

0.012

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

L;L;L;L;L;L;.;.

PhyloP100

-0.96

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.3

N;D;N;N;D;.;.;.

REVEL

Benign

0.091

Sift

Benign

0.67

T;T;T;T;T;.;.;.

Sift4G

Benign

0.26

T;T;T;T;T;T;T;.

Polyphen

0.017

B;B;B;B;B;.;.;.

Vest4

0.047

MutPred

0.36

Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);.;.;

MPC

0.20

ClinPred

0.0066

GERP RS

-5.0

Varity_R

0.35

gMVP

0.57

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over