Variant 19-41686921-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001291485.2(CEACAM7):c.365C>A(p.Thr122Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000697 in 1,434,874 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 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)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

CEACAM7
NM_001291485.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.109

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 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 linkuse as main transcript	c.365C>A	p.Thr122Asn	missense_variant	2/5	ENST00000401731.6	NP_001278414.1	Q14002-1
CEACAM7	NM_006890.5 linkuse as main transcript	c.365C>A	p.Thr122Asn	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.365C>A	p.Thr122Asn	missense_variant	2/5	2	NM_001291485.2	ENSP00000385932.1	Q14002-1
CEACAM7	ENST00000006724.7 linkuse as main transcript	c.365C>A	p.Thr122Asn	missense_variant	2/5	1		ENSP00000006724.3	Q14002-1
CEACAM7	ENST00000602225.1 linkuse as main transcript	c.365C>A	p.Thr122Asn	missense_variant	2/3	1		ENSP00000469597.1	Q14002-2A0A0A0MTT6
CEACAM7	ENST00000599715.1 linkuse as main transcript	n.461C>A		non_coding_transcript_exon_variant	3/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000176

AC:

AN:

227854

Hom.:

AF XY:

0.00000816

AC XY:

AN XY:

122594

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000644

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000100

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000697

AC:

AN:

1434874

Hom.:

Cov.:

AF XY:

0.00000421

AC XY:

AN XY:

712470

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000115

Gnomad4 NFE exome

AF:

9.09e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

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

Nov 09, 2022

The c.365C>A (p.T122N) alteration is located in exon 2 (coding exon 2) of the CEACAM7 gene. This alteration results from a C to A substitution at nucleotide position 365, causing the threonine (T) at amino acid position 122 to be replaced by an asparagine (N). 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

Uncertain

0.50

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.46

.;.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.67

.;.;T

M_CAP

Benign

0.0042

MetaRNN

Uncertain

0.54

D;D;D

MetaSVM

Benign

-0.53

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-4.0

D;D;.

REVEL

Benign

0.16

Sift

Benign

0.076

T;T;.

Sift4G

Uncertain

0.0090

D;D;D

Vest4

0.36

MutPred

0.58

Gain of catalytic residue at T122 (P = 0.0365);Gain of catalytic residue at T122 (P = 0.0365);Gain of catalytic residue at T122 (P = 0.0365);

MVP

0.55

MPC

0.11

ClinPred

0.41

GERP RS

0.61

gMVP

0.41

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