NM_004363.6:c.210T>G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_004363.6(CEACAM5):​c.210T>G​(p.Gly70Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 1,613,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G70G) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CEACAM5 NM_004363.6 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP7: Synonymous conserved (PhyloP=-1.33 with no splicing effect.

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>G	p.Gly70Gly	synonymous	Exon 2 of 10	NP_004354.3	A0A024R0K5
	CEACAM5	NM_001291484.3		c.210T>G	p.Gly70Gly	synonymous	Exon 2 of 10	NP_001278413.1	P06731-1
	CEACAM5	NM_001308398.3		c.210T>G	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>G	p.Gly70Gly	synonymous	Exon 2 of 10	ENSP00000221992.5	P06731-1
	CEACAM5	ENST00000405816.5	TSL:1	c.210T>G	p.Gly70Gly	synonymous	Exon 2 of 10	ENSP00000385072.1	P06731-1
	CEACAM5	ENST00000617332.4	TSL:1	c.210T>G	p.Gly70Gly	synonymous	Exon 2 of 9	ENSP00000482303.1	P06731-1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 151690 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000387

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000112 AC: 28 AN: 251066 AF XY: 0.000125

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000260

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000150

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000121 AC: 177 AN: 1461874 Hom.: 0 Cov.: 34 AF XY: 0.000111 AC XY: 81 AN XY: 727244

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000246 AC: 11 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000135 AC: 150 AN: 1111994

Other (OTH) AF: 0.000199 AC: 12 AN: 60396

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000105 AC: 16 AN: 151808 Hom.: 0 Cov.: 31 AF XY: 0.0000809 AC XY: 6 AN XY: 74182

African (AFR) AF: 0.0000484 AC: 2 AN: 41340

American (AMR) AF: 0.000262 AC: 4 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000388 AC: 2 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10520

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 67940

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.0000247 Hom.: 622

EpiCase AF: 0.000109

EpiControl AF: 0.000296

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.30
DANN	Benign	0.27
PhyloP100		-1.3
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism

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: COSV55754032; COSMIC: COSV55754032;