Genetic Variant NM_001817.4:c.394G>C (chr19-41625631-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001817.4(CEACAM4):c.394G>C(p.Asp132His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,436,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D132N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CEACAM4
NM_001817.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.612

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10868999).

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.394G>C	p.Asp132His	missense	Exon 2 of 7	NP_001808.2	O75871
CEACAM4	NM_001362495.2		c.394G>C	p.Asp132His	missense	Exon 2 of 6	NP_001349424.1	A0A077JIU5
CEACAM4	NM_001362492.2		c.394G>C	p.Asp132His	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.394G>C	p.Asp132His	missense	Exon 2 of 7	ENSP00000221954.2	O75871
CEACAM4	ENST00000600925.1	TSL:2	c.394G>C	p.Asp132His	missense	Exon 2 of 6	ENSP00000473018.1	M0R363
CEACAM4	ENST00000902906.1		c.64+1269G>C		intron	N/A	ENSP00000572965.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000139

AC:

AN:

1436088

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

711376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32926

American (AMR)

AF:

0.00

AC:

AN:

43070

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24014

East Asian (EAS)

AF:

0.00

AC:

AN:

39502

South Asian (SAS)

AF:

0.00

AC:

AN:

81790

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5614

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1097560

Other (OTH)

AF:

0.00

AC:

AN:

59322

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.0099

M_CAP

Benign

0.0044

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.90

PhyloP100

-0.61

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.4

REVEL

Benign

0.10

Sift

Uncertain

0.010

Sift4G

Uncertain

0.022

Polyphen

0.98

Vest4

0.14

MutPred

0.36

Gain of disorder (P = 0.0977)

MVP

0.27

MPC

0.040

ClinPred

0.24

GERP RS

-0.62

Varity_R

0.11

gMVP

0.31

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over