NM_002483.7:c.716T>C

Variant names:

• chr19-41761981-T-C
• rs11548735
• NM_002483.7:c.716T>C

Variant summary

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

The NM_002483.7(CEACAM6):​c.716T>C​(p.Val239Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 151,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 31)
• Consequence: CEACAM6 NM_002483.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149
• Publications: 32 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

ENSG00000268833 (HGNC:):

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=0.051127195).

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.716T>C	p.Val239Ala	missense	Exon 4 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.716T>C	p.Val239Ala	missense	Exon 4 of 6	ENSP00000199764.6	P40199
	CEACAM6	ENST00000890871.1		c.707T>C	p.Val236Ala	missense	Exon 4 of 6	ENSP00000560930.1
	CEACAM6	ENST00000943164.1		c.617T>C	p.Val206Ala	missense	Exon 4 of 6	ENSP00000613223.1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151496 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000148

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 55

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151496 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73928

African (AFR) AF: 0.0000242 AC: 1 AN: 41258

American (AMR) AF: 0.00 AC: 0 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67794

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 17102

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
CADD	Benign	0.012
MetaRNN	Benign	0.051	T
PhyloP100		-0.15
Sift4G	Benign	0.99	T
Vest4		0.022
gMVP		0.44

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: rs11548735;