rs1805223

Variant names:

• chr19-41756661-G-A
• rs1805223
• NM_002483.7:c.126G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_002483.7(CEACAM6):​c.126G>A​(p.Pro42Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.289 in 1,613,802 control chromosomes in the GnomAD database, including 68,916 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 0.26 (5478 hom., cov: 31)
  • Exomes 𝑓: 0.29 (63438 hom.)
• Consequence: CEACAM6 NM_002483.7 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• Publications: 17 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

ENSG00000267881 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-2.65 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.318 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM6	NM_002483.7	MANE Select	c.126G>A	p.Pro42Pro	synonymous	Exon 2 of 6	NP_002474.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM6	ENST00000199764.7	TSL:1 MANE Select	c.126G>A	p.Pro42Pro	synonymous	Exon 2 of 6	ENSP00000199764.6	P40199
	ENSG00000267881	ENST00000435837.2	TSL:3	c.126G>A	p.Pro42Pro	synonymous	Exon 2 of 2	ENSP00000469926.1	M0QYM2
	CEACAM6	ENST00000890871.1		c.126G>A	p.Pro42Pro	synonymous	Exon 2 of 6	ENSP00000560930.1

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39379 AN: 151822 Hom.: 5481 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.317

Gnomad EAS AF: 0.279

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.262

GnomAD2 exomes AF: 0.300 AC: 75499 AN: 251440 AF XY: 0.302

Gnomad AFR exome AF: 0.154

Gnomad AMR exome AF: 0.334

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.294

Gnomad FIN exome AF: 0.337

Gnomad NFE exome AF: 0.296

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.292 AC: 427155 AN: 1461862 Hom.: 63438 Cov.: 46 AF XY: 0.293 AC XY: 213226 AN XY: 727228

African (AFR) AF: 0.154 AC: 5146 AN: 33480

American (AMR) AF: 0.326 AC: 14558 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.324 AC: 8460 AN: 26122

East Asian (EAS) AF: 0.255 AC: 10129 AN: 39700

South Asian (SAS) AF: 0.322 AC: 27813 AN: 86256

European-Finnish (FIN) AF: 0.335 AC: 17920 AN: 53420

Middle Eastern (MID) AF: 0.382 AC: 2205 AN: 5768

European-Non Finnish (NFE) AF: 0.291 AC: 323236 AN: 1112002

Other (OTH) AF: 0.293 AC: 17688 AN: 60392

GnomAD4 genome AF: 0.259 AC: 39399 AN: 151940 Hom.: 5478 Cov.: 31 AF XY: 0.263 AC XY: 19490 AN XY: 74214

African (AFR) AF: 0.156 AC: 6484 AN: 41442

American (AMR) AF: 0.277 AC: 4240 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.317 AC: 1097 AN: 3458

East Asian (EAS) AF: 0.279 AC: 1437 AN: 5154

South Asian (SAS) AF: 0.332 AC: 1597 AN: 4816

European-Finnish (FIN) AF: 0.347 AC: 3647 AN: 10520

Middle Eastern (MID) AF: 0.380 AC: 111 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19992 AN: 67954

Other (OTH) AF: 0.261 AC: 551 AN: 2110

Alfa AF: 0.281 Hom.: 2735

Bravo AF: 0.250

Asia WGS AF: 0.303 AC: 1054 AN: 3478

EpiCase AF: 0.296

EpiControl AF: 0.288

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.9
DANN	Benign	0.53
PhyloP100		-2.6
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: rs1805223; hg19: chr19-42260569; COSMIC: COSV52266496; COSMIC: COSV52266496;