NM_004363.6:c.153G>T

Variant names:

• chr19-41709768-G-T
• rs150428325
• NM_004363.6:c.153G>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_004363.6(CEACAM5):​c.153G>T​(p.Val51Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00165 in 1,614,142 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0083 (11 hom., cov: 31)
  • Exomes 𝑓: 0.00095 (21 hom.)
• Consequence: CEACAM5 NM_004363.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.10
• Publications: 1 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 (REVEL=0.005).
• BP6: Variant 19-41709768-G-T is Benign according to our data. Variant chr19-41709768-G-T is described in ClinVar as Benign. ClinVar VariationId is 777478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.1 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00832 (1267/152280) while in subpopulation AFR AF = 0.0283 (1177/41536). AF 95% confidence interval is 0.027. There are 11 homozygotes in GnomAd4. There are 586 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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.153G>T	p.Val51Val	synonymous	Exon 2 of 10	NP_004354.3	A0A024R0K5
	CEACAM5	NM_001291484.3		c.153G>T	p.Val51Val	synonymous	Exon 2 of 10	NP_001278413.1	P06731-1
	CEACAM5	NM_001308398.3		c.153G>T	p.Val51Val	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.153G>T	p.Val51Val	synonymous	Exon 2 of 10	ENSP00000221992.5	P06731-1
	CEACAM5	ENST00000405816.5	TSL:1	c.153G>T	p.Val51Val	synonymous	Exon 2 of 10	ENSP00000385072.1	P06731-1
	CEACAM5	ENST00000617332.4	TSL:1	c.153G>T	p.Val51Val	synonymous	Exon 2 of 9	ENSP00000482303.1	P06731-1

Frequencies

GnomAD3 genomes AF: 0.00831 AC: 1264 AN: 152160 Hom.: 11 Cov.: 31

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00621

GnomAD2 exomes AF: 0.00227 AC: 572 AN: 251466 AF XY: 0.00172

Gnomad AFR exome AF: 0.0296

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00196

GnomAD4 exome AF: 0.000951 AC: 1390 AN: 1461862 Hom.: 21 Cov.: 32 AF XY: 0.000854 AC XY: 621 AN XY: 727240

African (AFR) AF: 0.0307 AC: 1026 AN: 33466

American (AMR) AF: 0.00172 AC: 77 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000696 AC: 6 AN: 86258

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

Middle Eastern (MID) AF: 0.00572 AC: 33 AN: 5768

European-Non Finnish (NFE) AF: 0.000106 AC: 118 AN: 1112004

Other (OTH) AF: 0.00215 AC: 130 AN: 60390

GnomAD4 genome AF: 0.00832 AC: 1267 AN: 152280 Hom.: 11 Cov.: 31 AF XY: 0.00787 AC XY: 586 AN XY: 74450

African (AFR) AF: 0.0283 AC: 1177 AN: 41536

American (AMR) AF: 0.00444 AC: 68 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68026

Other (OTH) AF: 0.00615 AC: 13 AN: 2114

Alfa AF: 0.00348 Hom.: 5

Bravo AF: 0.00977

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.000327

EpiControl AF: 0.000533

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	-0.99
CADD	Benign	0.24
DANN	Benign	0.49
PhyloP100		-2.1
PromoterAI		0.0056	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: rs150428325; hg19: chr19-42213687;