19-41709825-T-C

Variant names:

• chr19-41709825-T-C
• rs10402825
• NM_004363.6:c.210T>C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_004363.6(CEACAM5):​c.210T>C​(p.Gly70Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,613,572 control chromosomes in the GnomAD database, including 24,126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (3363 hom., cov: 31)
  • Exomes 𝑓: 0.16 (20763 hom.)
• Consequence: CEACAM5 NM_004363.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.33

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BP6: Variant 19-41709825-T-C is Benign according to our data. Variant chr19-41709825-T-C is described in ClinVar as [Benign]. Clinvar id is 770659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM5	NM_004363.6	c.210T>C	p.Gly70Gly	synonymous_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.210T>C	p.Gly70Gly	synonymous_variant	Exon 2 of 10	1	NM_004363.6	ENSP00000221992.5
ENSG00000267881	ENST00000435837.2	c.64+1030T>C		intron_variant	Intron 1 of 1	3		ENSP00000469926.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29227 AN: 151618 Hom.: 3351 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.111

Gnomad ASJ AF: 0.0880

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0326

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.150

GnomAD3 exomes AF: 0.135 AC: 33780 AN: 251066 Hom.: 3301 AF XY: 0.129 AC XY: 17541 AN XY: 135712

Gnomad AFR exome AF: 0.299

Gnomad AMR exome AF: 0.0669

Gnomad ASJ exome AF: 0.0818

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0280

Gnomad FIN exome AF: 0.252

Gnomad NFE exome AF: 0.165

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.158 AC: 231296 AN: 1461836 Hom.: 20763 Cov.: 34 AF XY: 0.154 AC XY: 111692 AN XY: 727232

Gnomad4 AFR exome AF: 0.296

Gnomad4 AMR exome AF: 0.0718

Gnomad4 ASJ exome AF: 0.0797

Gnomad4 EAS exome AF: 0.000252

Gnomad4 SAS exome AF: 0.0302

Gnomad4 FIN exome AF: 0.248

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.144

GnomAD4 genome AF: 0.193 AC: 29277 AN: 151736 Hom.: 3363 Cov.: 31 AF XY: 0.190 AC XY: 14066 AN XY: 74138

Gnomad4 AFR AF: 0.303

Gnomad4 AMR AF: 0.111

Gnomad4 ASJ AF: 0.0880

Gnomad4 EAS AF: 0.000969

Gnomad4 SAS AF: 0.0327

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.170

Gnomad4 OTH AF: 0.148

Alfa AF: 0.146 Hom.: 622

Bravo AF: 0.183

EpiCase AF: 0.143

EpiControl AF: 0.141

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
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.35

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: rs10402825; hg19: chr19-42213744;