19-41756657-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 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. 14/19 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

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0330244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM6	NM_002483.7	c.122C>T	p.Thr41Met	missense_variant	2/6	ENST00000199764.7
CEACAM6	XM_011526990.3	c.122C>T	p.Thr41Met	missense_variant	2/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM6	ENST00000199764.7	c.122C>T	p.Thr41Met	missense_variant	2/6	1	NM_002483.7	P1
CEACAM6	ENST00000595740.1			downstream_gene_variant		4

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

GnomAD3 exomes AF: 0.000517 AC: 130 AN: 251436 Hom.: 0 AF XY: 0.000515 AC XY: 70 AN XY: 135882

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 SAS exome AF: 0.000131

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

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.0000894

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.000543

Gnomad4 NFE exome AF: 0.00112

Gnomad4 OTH exome AF: 0.000762

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

Gnomad4 AFR AF: 0.000169

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00106

Gnomad4 OTH AF: 0.00

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

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2023

The c.122C>T (p.T41M) alteration is located in exon 2 (coding exon 2) of the CEACAM6 gene. This alteration results from a C to T substitution at nucleotide position 122, causing the threonine (T) at amino acid position 41 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.21	T
Sift4G	Benign	0.33	T;T
Vest4		0.072
MVP		0.17
MPC		0.17
ClinPred		0.014	T
GERP RS		-3.2
gMVP		0.19

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

Publications

LitVar

Other links and lift over

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