chr19-41687147-C-G

Position:

• chr19-41687147-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001291485.2(CEACAM7):​c.139G>C​(p.Glu47Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CEACAM7 NM_001291485.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.897

Genes affected

CEACAM7 (HGNC:1819): (CEA cell adhesion molecule 7) This gene encodes a cell surface glycoprotein and member of the carcinoembryonic antigen (CEA) family of proteins. Expression of this gene may be downregulated in colon and rectal cancer. Additionally, lower expression levels of this gene may be predictive of rectal cancer recurrence. This gene is present in a CEA family gene cluster on chromosome 19. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM7	NM_001291485.2	c.139G>C	p.Glu47Gln	missense_variant	2/5	ENST00000401731.6	NP_001278414.1
CEACAM7	NM_006890.5	c.139G>C	p.Glu47Gln	missense_variant	2/5		NP_008821.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CEACAM7	ENST00000401731.6	c.139G>C	p.Glu47Gln	missense_variant	2/5	2	NM_001291485.2	ENSP00000385932.1
CEACAM7	ENST00000006724.7	c.139G>C	p.Glu47Gln	missense_variant	2/5	1		ENSP00000006724.3
CEACAM7	ENST00000602225.1	c.139G>C	p.Glu47Gln	missense_variant	2/3	1		ENSP00000469597.1
CEACAM7	ENST00000599715.1	n.235G>C		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Nov 24, 2024

The c.139G>C (p.E47Q) alteration is located in exon 2 (coding exon 2) of the CEACAM7 gene. This alteration results from a G to C substitution at nucleotide position 139, causing the glutamic acid (E) at amino acid position 47 to be replaced by a glutamine (Q). 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	0.17
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.29	.;.;T
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.82	.;.;T
M_CAP	Benign	0.0053	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.56	T
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.6	D;D;.
REVEL	Benign	0.20
Sift	Uncertain	0.0080	D;D;.
Sift4G	Uncertain	0.022	D;D;D
Vest4		0.20
MutPred		0.80		Gain of catalytic residue at E47 (P = 0.1124);Gain of catalytic residue at E47 (P = 0.1124);Gain of catalytic residue at E47 (P = 0.1124);
MVP		0.64
MPC		0.096
ClinPred		0.80	D
GERP RS		1.7
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-42191078;