19-41709922-C-T

Variant names:

• chr19-41709922-C-T
• rs74626868
• NM_004363.6:c.307C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004363.6(CEACAM5):​c.307C>T​(p.Pro103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000895 in 1,614,004 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0047 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00050 (3 hom.)
• Consequence: CEACAM5 NM_004363.6 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.570

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0055286586).
• BP6: Variant 19-41709922-C-T is Benign according to our data. Variant chr19-41709922-C-T is described in ClinVar as [Benign]. Clinvar id is 775412.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00471 (716/152126) while in subpopulation AFR AF= 0.0165 (683/41484). AF 95% confidence interval is 0.0154. There are 4 homozygotes in gnomad4. There are 329 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM5	NM_004363.6	c.307C>T	p.Pro103Ser	missense_variant	Exon 2 of 10	ENST00000221992.11	NP_004354.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM5	ENST00000221992.11	c.307C>T	p.Pro103Ser	missense_variant	Exon 2 of 10	1	NM_004363.6	ENSP00000221992.5
ENSG00000267881	ENST00000435837.2	c.64+1127C>T		intron_variant	Intron 1 of 1	3		ENSP00000469926.1

Frequencies

GnomAD3 genomes AF: 0.00466 AC: 709 AN: 152008 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0163

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00336

GnomAD3 exomes AF: 0.00111 AC: 278 AN: 251450 Hom.: 0 AF XY: 0.000780 AC XY: 106 AN XY: 135890

Gnomad AFR exome AF: 0.0147

Gnomad AMR exome AF: 0.000954

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000352

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000499 AC: 729 AN: 1461878 Hom.: 3 Cov.: 34 AF XY: 0.000447 AC XY: 325 AN XY: 727246

Gnomad4 AFR exome AF: 0.0161

Gnomad4 AMR exome AF: 0.00119

Gnomad4 ASJ exome AF: 0.0000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000174

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.00157

GnomAD4 genome AF: 0.00471 AC: 716 AN: 152126 Hom.: 4 Cov.: 32 AF XY: 0.00442 AC XY: 329 AN XY: 74376

Gnomad4 AFR AF: 0.0165

Gnomad4 AMR AF: 0.00131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00195 Hom.: 0

Bravo AF: 0.00552

ESP6500AA AF: 0.0141 AC: 62

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00138 AC: 168

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 08, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.029
DANN	Benign	0.32
DEOGEN2	Benign	0.030	.;T;T;T;T;T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.42	.;.;T;T;T;.;.
MetaRNN	Benign	0.0055	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.2	.;N;.;.;.;N;.
REVEL	Benign	0.035
Sift	Benign	0.77	.;T;.;.;.;T;.
Sift4G	Benign	0.76	T;T;T;T;T;T;T
Vest4		0.046
MVP		0.17
MPC		0.33
ClinPred		0.064	T
GERP RS		-2.3
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs74626868; hg19: chr19-42213841;