chr19-42522175-C-T

Variant names:

• chr19-42522175-C-T
• rs535882194
• NM_001712.5:c.452G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001712.5(CEACAM1):​c.452G>A​(p.Ser151Asn) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEACAM1 NM_001712.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.342
• Publications: 0 publications found

Genes affected

CEACAM1 (HGNC:1814): (CEA cell adhesion molecule 1) This gene encodes a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin superfamily. Two subgroups of the CEA family, the CEA cell adhesion molecules and the pregnancy-specific glycoproteins, are located within a 1.2 Mb cluster on the long arm of chromosome 19. Eleven pseudogenes of the CEA cell adhesion molecule subgroup are also found in the cluster. The encoded protein was originally described in bile ducts of liver as biliary glycoprotein. Subsequently, it was found to be a cell-cell adhesion molecule detected on leukocytes, epithelia, and endothelia. The encoded protein mediates cell adhesion via homophilic as well as heterophilic binding to other proteins of the subgroup. Multiple cellular activities have been attributed to the encoded protein, including roles in the differentiation and arrangement of tissue three-dimensional structure, angiogenesis, apoptosis, tumor suppression, metastasis, and the modulation of innate and adaptive immune responses. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature of all variants has not been defined. [provided by RefSeq, May 2010]

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

ACMG classification

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=0.15080172).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001712.5. 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
	CEACAM1	NM_001712.5	MANE Select	c.452G>A	p.Ser151Asn	missense	Exon 3 of 9	NP_001703.2
	CEACAM1	NM_001205344.2		c.452G>A	p.Ser151Asn	missense	Exon 3 of 8	NP_001192273.1	P13688-10
	CEACAM1	NM_001024912.3		c.452G>A	p.Ser151Asn	missense	Exon 3 of 8	NP_001020083.1	P13688-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM1	ENST00000161559.11	TSL:1 MANE Select	c.452G>A	p.Ser151Asn	missense	Exon 3 of 9	ENSP00000161559.6	P13688-1
	CEACAM1	ENST00000403444.7	TSL:1	c.452G>A	p.Ser151Asn	missense	Exon 3 of 8	ENSP00000384709.3	P13688-8
	CEACAM1	ENST00000358394.7	TSL:1	c.452G>A	p.Ser151Asn	missense	Exon 3 of 9	ENSP00000351165.2	P13688-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	11
DANN	Benign	0.89
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.34
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.071
Sift	Uncertain	0.0090	D
Sift4G	Uncertain	0.046	D
Polyphen		0.97	D
Vest4		0.14
MutPred		0.28		Loss of glycosylation at S151 (P = 0.0516)
MVP		0.37
MPC		0.65
ClinPred		0.24	T
GERP RS		-0.56
Varity_R		0.18
gMVP		0.44
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs535882194; hg19: chr19-43026327;