ENST00000435837.2:c.65-3902A>C

Variant names:

• chr19-41752698-A-C
• rs3764577
• ENST00000435837.2:c.65-3902A>C

Variant summary

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

The ENST00000435837.2(ENSG00000267881):​c.65-3902A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 151,978 control chromosomes in the GnomAD database, including 11,681 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 (11681 hom., cov: 31)
• Consequence: ENSG00000267881 ENST00000435837.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.138
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.438 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.65-3902A>C		intron	N/A	ENSP00000469926.1
	CEACAM6	ENST00000595740.1	TSL:4	c.-120+950A>C		intron	N/A	ENSP00000469752.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59080 AN: 151860 Hom.: 11661 Cov.: 31

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.303

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.378

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.367

Gnomad OTH AF: 0.360

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

GnomAD4 genome AF: 0.389 AC: 59148 AN: 151978 Hom.: 11681 Cov.: 31 AF XY: 0.389 AC XY: 28912 AN XY: 74298

African (AFR) AF: 0.444 AC: 18388 AN: 41436

American (AMR) AF: 0.405 AC: 6180 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1143 AN: 3458

East Asian (EAS) AF: 0.303 AC: 1566 AN: 5160

South Asian (SAS) AF: 0.352 AC: 1695 AN: 4814

European-Finnish (FIN) AF: 0.378 AC: 3994 AN: 10564

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.367 AC: 24942 AN: 67954

Other (OTH) AF: 0.358 AC: 756 AN: 2112

Alfa AF: 0.374 Hom.: 8187

Bravo AF: 0.393

Asia WGS AF: 0.341 AC: 1187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	5.4
DANN	Benign	0.53
PhyloP100		-0.14

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: rs3764577; hg19: chr19-42256606;