Genetic Variant CEACAM4:p.Gly151Arg (chr19-41621742-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001817.4(CEACAM4):c.451G>C(p.Gly151Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

CEACAM4
NM_001817.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.16

Variant links:

Genes affected

CEACAM4 (HGNC:1816): (CEA cell adhesion molecule 4) Involved in phagocytosis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

CEACAM4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM4	NM_001817.4 link	c.451G>C	p.Gly151Arg	missense_variant	Exon 3 of 7	ENST00000221954.7	NP_001808.2	O75871

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM4	ENST00000221954.7 link	c.451G>C	p.Gly151Arg	missense_variant	Exon 3 of 7	1	NM_001817.4	ENSP00000221954.2		O75871
CEACAM4	ENST00000600925.1 link	c.451G>C	p.Gly151Arg	missense_variant	Exon 3 of 6	2		ENSP00000473018.1		M0R363

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249734

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135092

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1459862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726378

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 25, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.451G>C (p.G151R) alteration is located in exon 3 (coding exon 3) of the CEACAM4 gene. This alteration results from a G to C substitution at nucleotide position 451, causing the glycine (G) at amino acid position 151 to be replaced by an arginine (R). 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

Uncertain

0.34

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

DANN

Benign

0.87

DEOGEN2

Benign

0.034

T;.

Eigen

Benign

-0.011

Eigen_PC

Benign

-0.27

FATHMM_MKL

Benign

0.070

M_CAP

Benign

0.0021

MetaRNN

Uncertain

0.58

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

M;.

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.1

D;.

REVEL

Benign

0.056

Sift

Uncertain

0.0030

D;.

Sift4G

Benign

0.18

T;T

Polyphen

1.0

D;.

Vest4

0.61

MutPred

0.54

Loss of catalytic residue at V150 (P = 0.0648);Loss of catalytic residue at V150 (P = 0.0648);

MVP

0.59

MPC

0.031

ClinPred

0.33

GERP RS

3.3

Varity_R

0.12

gMVP

0.55

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