chr19-41709853-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004363.6(CEACAM5):c.238A>G(p.Ile80Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 1,613,712 control chromosomes in the GnomAD database, including 26,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I80T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.21 ( 4367 hom., cov: 31)

Exomes 𝑓: 0.16 ( 21721 hom. )

Consequence

CEACAM5
NM_004363.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.483

Publications

16 publications found

Variant links:

Genes affected

CEACAM5 (HGNC:1817): (CEA cell adhesion molecule 5) This gene encodes a cell surface glycoprotein that represents the founding member of the carcinoembryonic antigen (CEA) family of proteins. The encoded protein is used as a clinical biomarker for gastrointestinal cancers and may promote tumor development through its role as a cell adhesion molecule. Additionally, the encoded protein may regulate differentiation, apoptosis, and cell polarity. This gene is present in a CEA family gene cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

CEACAM5 links:

ENSG00000267881 (HGNC:):

ENSG00000267881 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023570955).

BP6

Variant 19-41709853-A-G is Benign according to our data. Variant chr19-41709853-A-G is described in ClinVar as Benign. ClinVar VariationId is 770660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004363.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEACAM5	NM_004363.6	MANE Select	c.238A>G	p.Ile80Val	missense	Exon 2 of 10	NP_004354.3	A0A024R0K5
CEACAM5	NM_001291484.3		c.238A>G	p.Ile80Val	missense	Exon 2 of 10	NP_001278413.1	P06731-1
CEACAM5	NM_001308398.3		c.238A>G	p.Ile80Val	missense	Exon 2 of 10	NP_001295327.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEACAM5	ENST00000221992.11	TSL:1 MANE Select	c.238A>G	p.Ile80Val	missense	Exon 2 of 10	ENSP00000221992.5	P06731-1
CEACAM5	ENST00000405816.5	TSL:1	c.238A>G	p.Ile80Val	missense	Exon 2 of 10	ENSP00000385072.1	P06731-1
CEACAM5	ENST00000617332.4	TSL:1	c.238A>G	p.Ile80Val	missense	Exon 2 of 9	ENSP00000482303.1	P06731-1

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32347

AN:

151790

Hom.:

4349

Cov.:

show subpopulations

Gnomad AFR

AF:

0.373

Gnomad AMI

AF:

0.0923

Gnomad AMR

AF:

0.120

Gnomad ASJ

AF:

0.0880

Gnomad EAS

AF:

0.000963

Gnomad SAS

AF:

0.0323

Gnomad FIN

AF:

0.254

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.170

Gnomad OTH

AF:

0.161

GnomAD2 exomes

AF:

0.139

AC:

34790

AN:

250392

AF XY:

0.133

show subpopulations

Gnomad AFR exome

AF:

0.369

Gnomad AMR exome

AF:

0.0711

Gnomad ASJ exome

AF:

0.0805

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.252

Gnomad NFE exome

AF:

0.164

Gnomad OTH exome

AF:

0.131

GnomAD4 exome

AF:

0.160

AC:

234598

AN:

1461804

Hom.:

21721

Cov.:

AF XY:

0.156

AC XY:

113103

AN XY:

727214

show subpopulations

African (AFR)

AF:

0.373

AC:

12496

AN:

33464

American (AMR)

AF:

0.0769

AC:

3438

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0796

AC:

2081

AN:

26134

East Asian (EAS)

AF:

0.000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0304

AC:

2622

AN:

86256

European-Finnish (FIN)

AF:

0.248

AC:

13233

AN:

53418

Middle Eastern (MID)

AF:

0.0435

AC:

251

AN:

5766

European-Non Finnish (NFE)

AF:

0.172

AC:

191435

AN:

1111952

Other (OTH)

AF:

0.150

AC:

9032

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

11149

22297

33446

44594

55743

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6716

13432

20148

26864

33580

<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:

0.213

AC:

32408

AN:

151908

Hom.:

4367

Cov.:

AF XY:

0.209

AC XY:

15539

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.374

AC:

15464

AN:

41348

American (AMR)

AF:

0.120

AC:

1830

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0880

AC:

305

AN:

3466

East Asian (EAS)

AF:

0.000965

AC:

AN:

5180

South Asian (SAS)

AF:

0.0324

AC:

156

AN:

4820

European-Finnish (FIN)

AF:

0.254

AC:

2680

AN:

10560

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.170

AC:

11539

AN:

67936

Other (OTH)

AF:

0.159

AC:

334

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1204

2408

3613

4817

6021

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

314

628

942

1256

1570

<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:

0.186

Hom.:

1353

Bravo

AF:

0.207

TwinsUK

AF:

0.174

AC:

645

ALSPAC

AF:

0.173

AC:

666

ESP6500AA

AF:

0.301

AC:

1325

ESP6500EA

AF:

0.124

AC:

1069

ExAC

AF:

0.145

AC:

17641

EpiCase

AF:

0.143

EpiControl

AF:

0.141

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.0030

(source)

DANN

Benign

0.15

DEOGEN2

Benign

0.0028

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00014

LIST_S2

Benign

0.069

MetaRNN

Benign

0.0024

MetaSVM

Benign

-0.93

PhyloP100

-0.48

PrimateAI

Benign

0.27

PROVEAN

Benign

0.33

REVEL

Benign

0.075

Sift

Benign

1.0

Sift4G

Benign

0.99

Vest4

0.019

MPC

0.18

ClinPred

0.0022

GERP RS

-1.3

PromoterAI

0.019

Neutral

(source)

gMVP

0.14

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over