19-41709737-C-T

Variant names:

• chr19-41709737-C-T
• rs111403501
• NM_004363.6:c.122C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004363.6(CEACAM5):​c.122C>T​(p.Thr41Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,614,120 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (1 hom.)
• Consequence: CEACAM5 NM_004363.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.654
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026494563).

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.122C>T	p.Thr41Met	missense	Exon 2 of 10	NP_004354.3	A0A024R0K5
	CEACAM5	NM_001291484.3		c.122C>T	p.Thr41Met	missense	Exon 2 of 10	NP_001278413.1	P06731-1
	CEACAM5	NM_001308398.3		c.122C>T	p.Thr41Met	missense	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.122C>T	p.Thr41Met	missense	Exon 2 of 10	ENSP00000221992.5	P06731-1
	CEACAM5	ENST00000405816.5	TSL:1	c.122C>T	p.Thr41Met	missense	Exon 2 of 10	ENSP00000385072.1	P06731-1
	CEACAM5	ENST00000617332.4	TSL:1	c.122C>T	p.Thr41Met	missense	Exon 2 of 9	ENSP00000482303.1	P06731-1

Frequencies

GnomAD3 genomes AF: 0.000210 AC: 32 AN: 152124 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000145

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000964

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000189

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.000151 AC: 38 AN: 251438 AF XY: 0.000162

Gnomad AFR exome AF: 0.000185

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000142 AC: 207 AN: 1461878 Hom.: 1 Cov.: 32 AF XY: 0.000150 AC XY: 109 AN XY: 727244

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.0000447 AC: 2 AN: 44722

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

East Asian (EAS) AF: 0.000302 AC: 12 AN: 39700

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86258

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53420

Middle Eastern (MID) AF: 0.00156 AC: 9 AN: 5768

European-Non Finnish (NFE) AF: 0.0000800 AC: 89 AN: 1111998

Other (OTH) AF: 0.00106 AC: 64 AN: 60396

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152242 Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16 AN XY: 74424

African (AFR) AF: 0.000168 AC: 7 AN: 41554

American (AMR) AF: 0.000196 AC: 3 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.000966 AC: 5 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.000189 AC: 2 AN: 10606

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.000153 Hom.: 0

Bravo AF: 0.000151

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000181 AC: 22

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000237

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.16
DANN	Benign	0.40
DEOGEN2	Benign	0.0085	T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.00040	N
LIST_S2	Benign	0.12	T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.026	T
MetaSVM	Benign	-0.98	T
PhyloP100		-0.65
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.91	N
REVEL	Benign	0.028
Sift	Benign	0.15	T
Sift4G	Benign	0.26	T
Vest4		0.066
MVP		0.31
MPC		0.25
ClinPred		0.010	T
GERP RS		-0.72
PromoterAI		-0.0026	Neutral
gMVP		0.23
Mutation Taster		=92/8	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: rs111403501; hg19: chr19-42213656; COSMIC: COSV99703996; COSMIC: COSV99703996;