rs374616817

Variant names:

• chr19-41756810-G-A
• rs374616817
• NM_002483.7:c.275G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-41756810-G-A
• chr19-41756810-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002483.7(CEACAM6):​c.275G>A​(p.Gly92Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G92V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEACAM6 NM_002483.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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]

LOC112268252 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.869

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM6	NM_002483.7	c.275G>A	p.Gly92Glu	missense_variant	Exon 2 of 6	ENST00000199764.7	NP_002474.4
CEACAM6	XM_011526990.3	c.275G>A	p.Gly92Glu	missense_variant	Exon 2 of 5		XP_011525292.1
LOC112268252	XR_002958447.2	n.1607C>T		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM6	ENST00000199764.7	c.275G>A	p.Gly92Glu	missense_variant	Exon 2 of 6	1	NM_002483.7	ENSP00000199764.6
ENSG00000267881	ENST00000435837.2	c.*73G>A		downstream_gene_variant		3		ENSP00000469926.1
CEACAM6	ENST00000595740.1	c.*175G>A		downstream_gene_variant		4		ENSP00000469752.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.75
BayesDel_addAF	Benign	-0.069	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	18
DANN	Uncertain	0.99
Eigen	Benign	-0.010
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.029	N
M_CAP	Benign	0.045	D
MetaRNN	Pathogenic	0.87	D
MetaSVM	Benign	-0.52	T
PrimateAI	Benign	0.26	T
PROVEAN	Pathogenic	-7.3	D
REVEL	Benign	0.15
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.018	D
Vest4		0.31
MutPred		0.85		Gain of phosphorylation at Y95 (P = 0.1135);
MVP		0.78
MPC		0.76
ClinPred		0.88	D
GERP RS		2.1
gMVP		0.52

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: rs374616817; hg19: chr19-42260718; COSMIC: COSV52269626; COSMIC: COSV52269626;