rs4803507

Variant names:

• chr19-41759642-G-A
• rs4803507
• NM_002483.7:c.425-1607G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002483.7(CEACAM6):​c.425-1607G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.266 in 152,034 control chromosomes in the GnomAD database, including 5,629 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5629 hom., cov: 32)
• Consequence: CEACAM6 NM_002483.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.579
• Publications: 3 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.32 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM6	NM_002483.7	c.425-1607G>A		intron_variant	Intron 2 of 5	ENST00000199764.7	NP_002474.4
CEACAM6	XM_011526990.3	c.425-1607G>A		intron_variant	Intron 2 of 4		XP_011525292.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM6	ENST00000199764.7	c.425-1607G>A		intron_variant	Intron 2 of 5	1	NM_002483.7	ENSP00000199764.6
ENSG00000268833	ENST00000601409.1	n.384-1561C>T		intron_variant	Intron 1 of 1	4
ENSG00000268833	ENST00000819470.1	n.111-1561C>T		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.266 AC: 40344 AN: 151916 Hom.: 5625 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.398

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.263

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.266 AC: 40383 AN: 152034 Hom.: 5629 Cov.: 32 AF XY: 0.267 AC XY: 19812 AN XY: 74304

African (AFR) AF: 0.208 AC: 8616 AN: 41466

American (AMR) AF: 0.277 AC: 4238 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3462

East Asian (EAS) AF: 0.111 AC: 575 AN: 5170

South Asian (SAS) AF: 0.334 AC: 1609 AN: 4818

European-Finnish (FIN) AF: 0.316 AC: 3334 AN: 10554

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 20014 AN: 67962

Other (OTH) AF: 0.263 AC: 555 AN: 2114

Alfa AF: 0.290 Hom.: 1231

Bravo AF: 0.259

Asia WGS AF: 0.244 AC: 848 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.9
DANN	Benign	0.46
PhyloP100		0.58
Mutation Taster		=100/0	polymorphism (auto)

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: rs4803507; hg19: chr19-42263550;