dbSNP rs8110904: CEACAM1:p.Ala83Val (chr19-42527217-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_001712.5(CEACAM1):c.248C>T(p.Ala83Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0184 in 1,613,440 control chromosomes in the GnomAD database, including 2,573 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.094 ( 1439 hom., cov: 32)

Exomes 𝑓: 0.011 ( 1134 hom. )

Consequence

CEACAM1
NM_001712.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.28

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 made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027994514).

BP6

Variant 19-42527217-G-A is Benign according to our data. Variant chr19-42527217-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM1	NM_001712.5 link	c.248C>T	p.Ala83Val	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.248C>T	p.Ala83Val	missense_variant	Exon 2 of 9	1	NM_001712.5	ENSP00000161559.6		P13688-1

Frequencies

GnomAD3 genomes

AF:

0.0936

AC:

14188

AN:

151598

Hom.:

1428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0443

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.00193

Gnomad OTH

AF:

0.0777

GnomAD3 exomes

AF:

0.0248

AC:

6228

AN:

251360

Hom.:

405

AF XY:

0.0182

AC XY:

2469

AN XY:

135880

show subpopulations

Gnomad AFR exome

AF:

0.318

Gnomad AMR exome

AF:

0.0196

Gnomad ASJ exome

AF:

0.00506

Gnomad EAS exome

AF:

0.000326

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00200

Gnomad OTH exome

AF:

0.0158

GnomAD4 exome

AF:

0.0106

AC:

15477

AN:

1461726

Hom.:

1134

Cov.:

AF XY:

0.00939

AC XY:

6829

AN XY:

727174

show subpopulations

Gnomad4 AFR exome

AF:

0.332

Gnomad4 AMR exome

AF:

0.0214

Gnomad4 ASJ exome

AF:

0.00455

Gnomad4 EAS exome

AF:

0.000327

Gnomad4 SAS exome

AF:

0.000974

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.00131

Gnomad4 OTH exome

AF:

0.0261

GnomAD4 genome

AF:

0.0939

AC:

14249

AN:

151714

Hom.:

1439

Cov.:

AF XY:

0.0901

AC XY:

6686

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.322

Gnomad4 AMR

AF:

0.0442

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00193

Gnomad4 OTH

AF:

0.0826

Alfa

AF:

0.0287

Hom.:

130

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.308

AC:

1359

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.0297

AC:

3612

Asia WGS

AF:

0.0510

AC:

176

AN:

3478

EpiCase

AF:

0.00234

EpiControl

AF:

0.00284

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.0040

DANN

Benign

0.55

DEOGEN2

Benign

0.064

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

Eigen

Benign

-2.1

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.054

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

MetaRNN

Benign

0.0028

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.3

N;N;N;N;N;N;.;.

PrimateAI

Benign

0.25

PROVEAN

Benign

2.3

N;N;N;N;N;.;.;.

REVEL

Benign

0.072

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.0010

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

Vest4

0.031

MPC

0.17

ClinPred

0.0026

GERP RS

-6.2

Varity_R

0.13

gMVP

0.098

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over