Genetic Variant CEACAM4:p.Ala127Thr (chr19-41625646-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001817.4(CEACAM4):c.379G>A(p.Ala127Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000187 in 1,600,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CEACAM4
NM_001817.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.57

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.037220776).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001817.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEACAM4	NM_001817.4	MANE Select	c.379G>A	p.Ala127Thr	missense	Exon 2 of 7	NP_001808.2	O75871
CEACAM4	NM_001362495.2		c.379G>A	p.Ala127Thr	missense	Exon 2 of 6	NP_001349424.1	A0A077JIU5
CEACAM4	NM_001362492.2		c.379G>A	p.Ala127Thr	missense	Exon 2 of 6	NP_001349421.1	A0A077JJN3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CEACAM4	ENST00000221954.7	TSL:1 MANE Select	c.379G>A	p.Ala127Thr	missense	Exon 2 of 7	ENSP00000221954.2	O75871
CEACAM4	ENST00000600925.1	TSL:2	c.379G>A	p.Ala127Thr	missense	Exon 2 of 6	ENSP00000473018.1	M0R363
CEACAM4	ENST00000902906.1		c.64+1254G>A		intron	N/A	ENSP00000572965.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000414

AC:

AN:

241530

AF XY:

0.00000768

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1448426

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33166

American (AMR)

AF:

0.00

AC:

AN:

43852

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24936

East Asian (EAS)

AF:

0.00

AC:

AN:

39588

South Asian (SAS)

AF:

0.00

AC:

AN:

84302

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52910

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5684

European-Non Finnish (NFE)

AF:

0.00000181

AC:

AN:

1104188

Other (OTH)

AF:

0.00

AC:

AN:

59800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000658

AC:

AN:

152080

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.000194

AC:

AN:

5162

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.023

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0018

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.00044

M_CAP

Benign

0.0042

MetaRNN

Benign

0.037

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.38

PhyloP100

-2.6

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.11

REVEL

Benign

0.011

Sift

Benign

0.46

Sift4G

Benign

0.50

Polyphen

0.0

Vest4

0.060

MutPred

0.20

Gain of glycosylation at A127 (P = 0.0857)

MVP

0.061

MPC

0.026

ClinPred

0.040

GERP RS

-3.6

Varity_R

0.024

gMVP

0.095

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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