Variant 19-41686913-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001291485.2(CEACAM7):c.373G>A(p.Val125Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,554,990 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

CEACAM7
NM_001291485.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.68

Variant links:

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]

CEACAM7 links:

CEACAM7 (HGNC:):

CEACAM7 links:

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ACMG classification

Classification made for transcript

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=0.03743252).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CEACAM7	NM_001291485.2 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	2/5	ENST00000401731.6	NP_001278414.1	Q14002-1
CEACAM7	NM_006890.5 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	2/5		NP_008821.2	Q14002-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CEACAM7	ENST00000401731.6 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	2/5	2	NM_001291485.2	ENSP00000385932.1	Q14002-1
CEACAM7	ENST00000006724.7 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	2/5	1		ENSP00000006724.3	Q14002-1
CEACAM7	ENST00000602225.1 linkuse as main transcript	c.373G>A	p.Val125Ile	missense_variant	2/3	1		ENSP00000469597.1	Q14002-2A0A0A0MTT6
CEACAM7	ENST00000599715.1 linkuse as main transcript	n.469G>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000245

AC:

AN:

204390

Hom.:

AF XY:

0.0000274

AC XY:

AN XY:

109494

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000302

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000998

AC:

AN:

1402744

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

693278

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000763

Gnomad4 SAS exome

AF:

0.0000133

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000276

Gnomad4 OTH exome

AF:

0.000121

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152246

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000113

ExAC

AF:

0.0000330

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 19, 2024

The c.373G>A (p.V125I) alteration is located in exon 2 (coding exon 2) of the CEACAM7 gene. This alteration results from a G to A substitution at nucleotide position 373, causing the valine (V) at amino acid position 125 to be replaced by an isoleucine (I). 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

0.083

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.049

DANN

Benign

0.27

DEOGEN2

Benign

0.010

.;.;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.64

.;.;T

M_CAP

Benign

0.0052

MetaRNN

Benign

0.037

T;T;T

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.39

N;N;.

REVEL

Benign

0.052

Sift

Benign

1.0

T;T;.

Sift4G

Benign

1.0

T;T;T

Vest4

0.16

MutPred

0.51

Gain of catalytic residue at L130 (P = 0.0394);Gain of catalytic residue at L130 (P = 0.0394);Gain of catalytic residue at L130 (P = 0.0394);

MVP

0.12

MPC

0.022

ClinPred

0.024

GERP RS

-3.4

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over