chr19-41757812-G-A

Variant names:

• chr19-41757812-G-A
• rs3795018
• NM_002483.7:c.424+853G>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.424+853G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 152,002 control chromosomes in the GnomAD database, including 8,146 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 0.32 (8145 hom., cov: 32)
  • Exomes 𝑓: 0.23 (1 hom.)
• Consequence: CEACAM6 NM_002483.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.515
• Publications: 5 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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM6	NM_002483.7	MANE Select	c.424+853G>A		intron	N/A	NP_002474.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM6	ENST00000199764.7	TSL:1 MANE Select	c.424+853G>A		intron	N/A	ENSP00000199764.6
	ENSG00000268833	ENST00000819471.1		n.615C>T		non_coding_transcript_exon	Exon 2 of 2
	ENSG00000268833	ENST00000601409.1	TSL:4	n.*86C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48947 AN: 151858 Hom.: 8132 Cov.: 32

Gnomad AFR AF: 0.324

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.514

Gnomad SAS AF: 0.477

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.304

GnomAD4 exome AF: 0.231 AC: 6 AN: 26 Hom.: 1 AF XY: 0.250 AC XY: 5 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.231 AC: 6 AN: 26

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.322 AC: 49002 AN: 151976 Hom.: 8145 Cov.: 32 AF XY: 0.329 AC XY: 24435 AN XY: 74268

African (AFR) AF: 0.324 AC: 13423 AN: 41432

American (AMR) AF: 0.297 AC: 4533 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1105 AN: 3458

East Asian (EAS) AF: 0.513 AC: 2648 AN: 5158

South Asian (SAS) AF: 0.478 AC: 2307 AN: 4822

European-Finnish (FIN) AF: 0.368 AC: 3888 AN: 10558

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.296 AC: 20082 AN: 67950

Other (OTH) AF: 0.311 AC: 655 AN: 2108

Alfa AF: 0.321 Hom.: 2751

Bravo AF: 0.316

Asia WGS AF: 0.501 AC: 1741 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	8.5
DANN	Benign	0.75
PhyloP100		0.52
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: rs3795018; hg19: chr19-42261720;