19-41686982-T-C

Variant names:

• chr19-41686982-T-C
• NM_001291485.2:c.304A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001291485.2(CEACAM7):​c.304A>G​(p.Ile102Val) 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 benign outcome for this variant. 15/19 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: -1.21

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 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=0.062436044).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM7	NM_001291485.2	c.304A>G	p.Ile102Val	missense_variant	Exon 2 of 5	ENST00000401731.6	NP_001278414.1
CEACAM7	NM_006890.5	c.304A>G	p.Ile102Val	missense_variant	Exon 2 of 5		NP_008821.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM7	ENST00000401731.6	c.304A>G	p.Ile102Val	missense_variant	Exon 2 of 5	2	NM_001291485.2	ENSP00000385932.1
CEACAM7	ENST00000006724.7	c.304A>G	p.Ile102Val	missense_variant	Exon 2 of 5	1		ENSP00000006724.3
CEACAM7	ENST00000602225.1	c.304A>G	p.Ile102Val	missense_variant	Exon 2 of 3	1		ENSP00000469597.1
CEACAM7	ENST00000599715.1	n.400A>G		non_coding_transcript_exon_variant	Exon 3 of 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

Feb 21, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.304A>G (p.I102V) alteration is located in exon 2 (coding exon 2) of the CEACAM7 gene. This alteration results from a A to G substitution at nucleotide position 304, causing the isoleucine (I) at amino acid position 102 to be replaced by a valine (V). 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	0.10
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.0050
DANN	Benign	0.30
DEOGEN2	Benign	0.0079	.;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0067	N
LIST_S2	Benign	0.49	.;.;T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.062	T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.48	N;N;.
REVEL	Benign	0.063
Sift	Benign	0.42	T;T;.
Sift4G	Benign	0.61	T;T;T
Vest4		0.043
MutPred		0.59		Loss of catalytic residue at P104 (P = 0.0298);Loss of catalytic residue at P104 (P = 0.0298);Loss of catalytic residue at P104 (P = 0.0298);
MVP		0.13
MPC		0.017
ClinPred		0.061	T
GERP RS		0.61
gMVP		0.13

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: chr19-42190913;