NM_002483.7:c.122C>T

Variant names:

• chr19-41756657-C-T
• rs149583724
• NM_002483.7:c.122C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002483.7(CEACAM6):​c.122C>T​(p.Thr41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00088 in 1,614,110 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00056 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00091 (1 hom.)
• Consequence: CEACAM6 NM_002483.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.827
• Publications: 1 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0330244).

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.122C>T	p.Thr41Met	missense	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.122C>T	p.Thr41Met	missense	Exon 2 of 6	ENSP00000199764.6	P40199
	ENSG00000267881	ENST00000435837.2	TSL:3	c.122C>T	p.Thr41Met	missense	Exon 2 of 2	ENSP00000469926.1	M0QYM2
	CEACAM6	ENST00000890871.1		c.122C>T	p.Thr41Met	missense	Exon 2 of 6	ENSP00000560930.1

Frequencies

GnomAD3 genomes AF: 0.000559 AC: 85 AN: 152114 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00106

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000517 AC: 130 AN: 251436 AF XY: 0.000515

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000416

Gnomad NFE exome AF: 0.000976

Gnomad OTH exome AF: 0.000489

GnomAD4 exome AF: 0.000913 AC: 1335 AN: 1461878 Hom.: 1 Cov.: 33 AF XY: 0.000892 AC XY: 649 AN XY: 727242

African (AFR) AF: 0.000149 AC: 5 AN: 33480

American (AMR) AF: 0.0000894 AC: 4 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86254

European-Finnish (FIN) AF: 0.000543 AC: 29 AN: 53420

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00112 AC: 1244 AN: 1112002

Other (OTH) AF: 0.000762 AC: 46 AN: 60396

GnomAD4 genome AF: 0.000558 AC: 85 AN: 152232 Hom.: 0 Cov.: 31 AF XY: 0.000524 AC XY: 39 AN XY: 74424

African (AFR) AF: 0.000169 AC: 7 AN: 41518

American (AMR) AF: 0.000196 AC: 3 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00106 AC: 72 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2114

Alfa AF: 0.000729 Hom.: 0

Bravo AF: 0.000536

TwinsUK AF: 0.00108 AC: 4

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.00151 AC: 13

ExAC AF: 0.000544 AC: 66

EpiCase AF: 0.000818

EpiControl AF: 0.000771

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	0.48
DANN	Benign	0.53
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00051	N
LIST_S2	Benign	0.082	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.033	T
MetaSVM	Benign	-1.0	T
PhyloP100		-0.83
PrimateAI	Benign	0.21	T
PROVEAN	Benign	0.63	N
REVEL	Benign	0.15
Sift	Benign	0.16	T
Sift4G	Benign	0.33	T
Vest4		0.072
MVP		0.17
MPC		0.17
ClinPred		0.014	T
GERP RS		-3.2
gMVP		0.19
Mutation Taster		=88/12	polymorphism

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: rs149583724; hg19: chr19-42260565; COSMIC: COSV52268776; COSMIC: COSV52268776;