rs10415946

Variant names:

• chr19-41755151-A-G
• rs10415946
• ENST00000435837.2:c.65-1449A>G

Variant summary

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

The ENST00000435837.2(ENSG00000267881):​c.65-1449A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 151,986 control chromosomes in the GnomAD database, including 11,555 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 0.39 (11555 hom., cov: 31)
• Consequence: ENSG00000267881 ENST00000435837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.152
• Publications: 7 publications found

Genes affected

ENSG00000267881 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000435837.2. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000267881	ENST00000435837.2	TSL:3	c.65-1449A>G		intron	N/A	ENSP00000469926.1
	CEACAM6	ENST00000595740.1	TSL:4	c.-119-369A>G		intron	N/A	ENSP00000469752.1

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58815 AN: 151868 Hom.: 11540 Cov.: 31

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.305

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.377

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.362

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

GnomAD4 genome AF: 0.387 AC: 58874 AN: 151986 Hom.: 11555 Cov.: 31 AF XY: 0.387 AC XY: 28782 AN XY: 74290

African (AFR) AF: 0.438 AC: 18133 AN: 41424

American (AMR) AF: 0.404 AC: 6166 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1150 AN: 3464

East Asian (EAS) AF: 0.306 AC: 1581 AN: 5170

South Asian (SAS) AF: 0.351 AC: 1693 AN: 4822

European-Finnish (FIN) AF: 0.377 AC: 3987 AN: 10562

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

European-Non Finnish (NFE) AF: 0.367 AC: 24919 AN: 67962

Other (OTH) AF: 0.360 AC: 760 AN: 2110

Alfa AF: 0.370 Hom.: 12323

Bravo AF: 0.390

Asia WGS AF: 0.340 AC: 1183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.8
DANN	Benign	0.34
PhyloP100		-0.15
PromoterAI		0.025	Neutral

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: rs10415946; hg19: chr19-42259059;