19-41619356-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001817.4(CEACAM4):​c.709G>A​(p.Asp237Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000744 in 1,613,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000075 ( 0 hom. )

Consequence

CEACAM4
NM_001817.4 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.844
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03853056).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CEACAM4NM_001817.4 linkc.709G>A p.Asp237Asn missense_variant Exon 7 of 7 ENST00000221954.7 NP_001808.2 O75871

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CEACAM4ENST00000221954.7 linkc.709G>A p.Asp237Asn missense_variant Exon 7 of 7 1 NM_001817.4 ENSP00000221954.2 O75871
CEACAM4ENST00000600925.1 linkc.*212G>A downstream_gene_variant 2 ENSP00000473018.1 M0R363

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
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
GnomAD3 exomes
AF:
0.00000796
AC:
2
AN:
251394
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135864
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000753
AC:
11
AN:
1461784
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727198
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000719
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152170
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.00000824
AC:
1
EpiCase
AF:
0.000164
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 11, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.709G>A (p.D237N) alteration is located in exon 7 (coding exon 7) of the CEACAM4 gene. This alteration results from a G to A substitution at nucleotide position 709, causing the aspartic acid (D) at amino acid position 237 to be replaced by an asparagine (N). 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
Benign
0.079
BayesDel_addAF
Benign
-0.56
T
BayesDel_noAF
Benign
-0.86
CADD
Benign
1.9
DANN
Benign
0.61
DEOGEN2
Benign
0.0014
T
Eigen
Benign
-1.2
Eigen_PC
Benign
-1.3
FATHMM_MKL
Benign
0.00083
N
M_CAP
Benign
0.0010
T
MetaRNN
Benign
0.039
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.81
L
PrimateAI
Benign
0.41
T
PROVEAN
Benign
0.10
N
REVEL
Benign
0.010
Sift
Benign
0.39
T
Sift4G
Benign
1.0
T
Polyphen
0.015
B
Vest4
0.047
MutPred
0.37
Gain of methylation at K239 (P = 0.0565);
MVP
0.23
MPC
0.18
ClinPred
0.054
T
GERP RS
-1.6
Varity_R
0.026
gMVP
0.029

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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.

Other links and lift over

dbSNP: rs782727802; hg19: chr19-42125729; COSMIC: COSV99701164; COSMIC: COSV99701164; API