rs10402825

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr19-41709825-T-C
• chr19-41709825-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 2P and 16B. PVS1_Moderate BP6_Very_Strong BA1

The NM_001440321.1(CEACAM5):​c.208+2T>C variant causes a splice donor, intron 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_001440321.1 splice_donor, intron
• 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 -14 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.07606973 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• 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.
• 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_001440321.1. 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;