19-41758983-G-T

Variant names:

• chr19-41758983-G-T
• rs3795020
• NM_002483.7:c.424+2024G>T

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+2024G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.321 in 152,086 control chromosomes in the GnomAD database, including 8,097 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 (8097 hom., cov: 32)
• Consequence: CEACAM6 NM_002483.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 4 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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.495 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM6	NM_002483.7	c.424+2024G>T		intron_variant	Intron 2 of 5	ENST00000199764.7	NP_002474.4
CEACAM6	XM_011526990.3	c.424+2024G>T		intron_variant	Intron 2 of 4		XP_011525292.1
LOC112268252	XR_002958447.2	n.335+44C>A		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM6	ENST00000199764.7	c.424+2024G>T		intron_variant	Intron 2 of 5	1	NM_002483.7	ENSP00000199764.6
ENSG00000268833	ENST00000601409.1	n.384-902C>A		intron_variant	Intron 1 of 1	4
ENSG00000268833	ENST00000819470.1	n.111-902C>A		intron_variant	Intron 1 of 1
ENSG00000268833	ENST00000819471.1	n.345+44C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.321 AC: 48826 AN: 151968 Hom.: 8085 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.323

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.297

Gnomad OTH AF: 0.302

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

GnomAD4 genome AF: 0.321 AC: 48880 AN: 152086 Hom.: 8097 Cov.: 32 AF XY: 0.328 AC XY: 24379 AN XY: 74328

African (AFR) AF: 0.319 AC: 13214 AN: 41488

American (AMR) AF: 0.296 AC: 4529 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.323 AC: 1117 AN: 3460

East Asian (EAS) AF: 0.511 AC: 2638 AN: 5162

South Asian (SAS) AF: 0.480 AC: 2312 AN: 4820

European-Finnish (FIN) AF: 0.367 AC: 3878 AN: 10562

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.297 AC: 20175 AN: 67986

Other (OTH) AF: 0.309 AC: 653 AN: 2116

Alfa AF: 0.308 Hom.: 30812

Bravo AF: 0.314

Asia WGS AF: 0.503 AC: 1745 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.33
DANN	Benign	0.61
PhyloP100		-1.1
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: rs3795020; hg19: chr19-42262891;