19-41619337-A-C

Variant names:

• chr19-41619337-A-C
• rs782007228
• NM_001817.4:c.728T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001817.4(CEACAM4):​c.728T>G​(p.Val243Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. V243A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEACAM4 NM_001817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.816
• Publications: 0 publications found

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]

ACMG classification

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=0.043201387).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM4	NM_001817.4	MANE Select	c.728T>G	p.Val243Gly	missense	Exon 7 of 7	NP_001808.2	O75871
	CEACAM4	NM_001362492.2		c.610T>G	p.Ser204Ala	missense	Exon 6 of 6	NP_001349421.1	A0A077JJN3
	CEACAM4	NM_001362493.2		c.368T>G	p.Val123Gly	missense	Exon 6 of 6	NP_001349422.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM4	ENST00000221954.7	TSL:1 MANE Select	c.728T>G	p.Val243Gly	missense	Exon 7 of 7	ENSP00000221954.2	O75871
	CEACAM4	ENST00000902906.1		c.368T>G	p.Val123Gly	missense	Exon 6 of 6	ENSP00000572965.1
	CEACAM4	ENST00000600925.1	TSL:2	c.*231T>G		downstream_gene	N/A	ENSP00000473018.1	M0R363

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.6
DANN	Benign	0.89
DEOGEN2	Benign	0.0039	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0017	N
M_CAP	Benign	0.00095	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.69	N
PhyloP100		-0.82
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.33	N
REVEL	Benign	0.0070
Sift	Uncertain	0.022	D
Sift4G	Uncertain	0.011	D
Polyphen		0.0	B
Vest4		0.046
MutPred		0.17		Loss of stability (P = 0.0076)
MVP		0.11
MPC		0.031
ClinPred		0.20	T
GERP RS		-3.7
Varity_R		0.039
gMVP		0.077
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs782007228; hg19: chr19-42125710;