NM_004363.6:c.210T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004363.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM5	NM_004363.6	MANE Select	c.210T>C	p.Gly70Gly	synonymous	Exon 2 of 10	NP_004354.3	A0A024R0K5
	CEACAM5	NM_001291484.3		c.210T>C	p.Gly70Gly	synonymous	Exon 2 of 10	NP_001278413.1	P06731-1
	CEACAM5	NM_001308398.3		c.210T>C	p.Gly70Gly	synonymous	Exon 2 of 10	NP_001295327.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM5	ENST00000221992.11	TSL:1 MANE Select	c.210T>C	p.Gly70Gly	synonymous	Exon 2 of 10	ENSP00000221992.5	P06731-1
	CEACAM5	ENST00000405816.5	TSL:1	c.210T>C	p.Gly70Gly	synonymous	Exon 2 of 10	ENSP00000385072.1	P06731-1
	CEACAM5	ENST00000617332.4	TSL:1	c.210T>C	p.Gly70Gly	synonymous	Exon 2 of 9	ENSP00000482303.1	P06731-1

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

GnomAD2 exomes AF: 0.135 AC: 33780 AN: 251066 AF XY: 0.129

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 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

African (AFR) AF: 0.296 AC: 9919 AN: 33462

American (AMR) AF: 0.0718 AC: 3211 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0797 AC: 2082 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0302 AC: 2601 AN: 86258

European-Finnish (FIN) AF: 0.248 AC: 13234 AN: 53420

Middle Eastern (MID) AF: 0.0418 AC: 241 AN: 5766

European-Non Finnish (NFE) AF: 0.172 AC: 191283 AN: 1111984

Other (OTH) AF: 0.144 AC: 8715 AN: 60390

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

African (AFR) AF: 0.303 AC: 12496 AN: 41294

American (AMR) AF: 0.111 AC: 1693 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.0880 AC: 305 AN: 3464

East Asian (EAS) AF: 0.000969 AC: 5 AN: 5158

South Asian (SAS) AF: 0.0327 AC: 157 AN: 4808

European-Finnish (FIN) AF: 0.255 AC: 2683 AN: 10510

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11530 AN: 67930

Other (OTH) AF: 0.148 AC: 313 AN: 2108

Alfa AF: 0.146 Hom.: 622

Bravo AF: 0.183

EpiCase AF: 0.143

EpiControl AF: 0.141

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.30
DANN	Benign	0.35
PhyloP100		-1.3
PromoterAI		-0.0060	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10402825; hg19: chr19-42213744; COSMIC: COSV108068154; COSMIC: COSV108068154;