19-41756690-T-A

Variant names:

• chr19-41756690-T-A
• NM_002483.7:c.155T>A

Variant summary

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

The NM_002483.7(CEACAM6):​c.155T>A​(p.Leu52His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEACAM6 NM_002483.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.156
• Publications: 0 publications found

Genes affected

CEACAM6 (HGNC:1818): (CEA cell adhesion molecule 6) This gene encodes a protein that belongs to the carcinoembryonic antigen (CEA) family whose members are glycosyl phosphatidyl inositol (GPI) anchored cell surface glycoproteins. Members of this family play a role in cell adhesion and are widely used as tumor markers in serum immunoassay determinations of carcinoma. This gene affects the sensitivity of tumor cells to adenovirus infection. The protein encoded by this gene acts as a receptor for adherent-invasive E. coli adhesion to the surface of ileal epithelial cells in patients with Crohn's disease. This gene is clustered with genes and pseudogenes of the cell adhesion molecules subgroup of the CEA family on chromosome 19. [provided by RefSeq, Apr 2014]

CEACAM6 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000267881 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002483.7. 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
	CEACAM6	NM_002483.7	MANE Select	c.155T>A	p.Leu52His	missense	Exon 2 of 6	NP_002474.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM6	ENST00000199764.7	TSL:1 MANE Select	c.155T>A	p.Leu52His	missense	Exon 2 of 6	ENSP00000199764.6	P40199
	ENSG00000267881	ENST00000435837.2	TSL:3	c.155T>A	p.Leu52His	missense	Exon 2 of 2	ENSP00000469926.1	M0QYM2
	CEACAM6	ENST00000890871.1		c.155T>A	p.Leu52His	missense	Exon 2 of 6	ENSP00000560930.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

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	0.23
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	16
DANN	Benign	0.94
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.032	D
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-0.40	T
PhyloP100		0.16
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-6.3	D
REVEL	Benign	0.18
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.036	D
Vest4		0.48
MutPred		0.73		Gain of disorder (P = 0.03)
MVP		0.63
MPC		0.33
ClinPred		0.32	T
GERP RS		1.5
gMVP		0.28
Mutation Taster		=64/36	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

hg19: chr19-42260598;