19-41709949-A-G

Variant names:

• chr19-41709949-A-G
• rs34155934
• NM_004363.6:c.334A>G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004363.6(CEACAM5):​c.334A>G​(p.Ile112Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 1,612,866 control chromosomes in the GnomAD database, including 23,525 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3020 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20505 hom.)
• Consequence: CEACAM5 NM_004363.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0770

Genes affected

CEACAM5 (HGNC:1817): (CEA cell adhesion molecule 5) This gene encodes a cell surface glycoprotein that represents the founding member of the carcinoembryonic antigen (CEA) family of proteins. The encoded protein is used as a clinical biomarker for gastrointestinal cancers and may promote tumor development through its role as a cell adhesion molecule. Additionally, the encoded protein may regulate differentiation, apoptosis, and cell polarity. 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]

ENSG00000267881 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0049575567).
• BP6: Variant 19-41709949-A-G is Benign according to our data. Variant chr19-41709949-A-G is described in ClinVar as [Benign]. Clinvar id is 770662.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.273 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM5	NM_004363.6	c.334A>G	p.Ile112Val	missense_variant	Exon 2 of 10	ENST00000221992.11	NP_004354.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM5	ENST00000221992.11	c.334A>G	p.Ile112Val	missense_variant	Exon 2 of 10	1	NM_004363.6	ENSP00000221992.5
ENSG00000267881	ENST00000435837.2	c.64+1154A>G		intron_variant	Intron 1 of 1	3		ENSP00000469926.1

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28154 AN: 151770 Hom.: 3018 Cov.: 31

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.110

Gnomad ASJ AF: 0.0880

Gnomad EAS AF: 0.000965

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.254

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.145

GnomAD3 exomes AF: 0.130 AC: 32506 AN: 249428 Hom.: 3126 AF XY: 0.125 AC XY: 16887 AN XY: 134758

Gnomad AFR exome AF: 0.276

Gnomad AMR exome AF: 0.0648

Gnomad ASJ exome AF: 0.0755

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0260

Gnomad FIN exome AF: 0.248

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.157 AC: 229973 AN: 1460978 Hom.: 20505 Cov.: 34 AF XY: 0.153 AC XY: 111027 AN XY: 726686

Gnomad4 AFR exome AF: 0.274

Gnomad4 AMR exome AF: 0.0703

Gnomad4 ASJ exome AF: 0.0792

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0299

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.142

GnomAD4 genome AF: 0.186 AC: 28181 AN: 151888 Hom.: 3020 Cov.: 31 AF XY: 0.182 AC XY: 13509 AN XY: 74218

Gnomad4 AFR AF: 0.277

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0880

Gnomad4 EAS AF: 0.000967

Gnomad4 SAS AF: 0.0319

Gnomad4 FIN AF: 0.254

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.143

Alfa AF: 0.171 Hom.: 1055

Bravo AF: 0.175

ESP6500AA AF: 0.248 AC: 1093

ESP6500EA AF: 0.150 AC: 1294

ExAC AF: 0.137 AC: 16676

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.026
DANN	Benign	0.21
DEOGEN2	Benign	0.0043	.;T;T;T;T;T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.00010	N
LIST_S2	Benign	0.59	.;.;T;T;T;.;.
MetaRNN	Benign	0.0050	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.62	.;N;.;.;.;N;.
REVEL	Benign	0.072
Sift	Benign	1.0	.;T;.;.;.;T;.
Sift4G	Benign	1.0	T;T;T;T;T;T;T
Vest4		0.018
MPC		0.17
ClinPred		0.0036	T
GERP RS		-0.94
gMVP		0.081

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: rs34155934; hg19: chr19-42213868; COSMIC: COSV55755266; COSMIC: COSV55755266;