19-42527096-T-G

Variant names:

• chr19-42527096-T-G
• rs8111468
• NM_001712.5:c.369A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001712.5(CEACAM1):​c.369A>C​(p.Gln123His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0194 in 1,582,376 control chromosomes in the GnomAD database, including 3,383 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.096 (1838 hom., cov: 32)
  • Exomes 𝑓: 0.011 (1545 hom.)
• Consequence: CEACAM1 NM_001712.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.961
• Publications: 13 publications found

Genes affected

CEACAM1 (HGNC:1814): (CEA cell adhesion molecule 1) This gene encodes a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin superfamily. Two subgroups of the CEA family, the CEA cell adhesion molecules and the pregnancy-specific glycoproteins, are located within a 1.2 Mb cluster on the long arm of chromosome 19. Eleven pseudogenes of the CEA cell adhesion molecule subgroup are also found in the cluster. The encoded protein was originally described in bile ducts of liver as biliary glycoprotein. Subsequently, it was found to be a cell-cell adhesion molecule detected on leukocytes, epithelia, and endothelia. The encoded protein mediates cell adhesion via homophilic as well as heterophilic binding to other proteins of the subgroup. Multiple cellular activities have been attributed to the encoded protein, including roles in the differentiation and arrangement of tissue three-dimensional structure, angiogenesis, apoptosis, tumor suppression, metastasis, and the modulation of innate and adaptive immune responses. Multiple transcript variants encoding different isoforms have been reported, but the full-length nature of all variants has not been defined. [provided by RefSeq, May 2010]

LIPE-AS1 (HGNC:48589): (LIPE antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011648744).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001712.5. 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
	CEACAM1	NM_001712.5	MANE Select	c.369A>C	p.Gln123His	missense	Exon 2 of 9	NP_001703.2
	CEACAM1	NM_001205344.2		c.369A>C	p.Gln123His	missense	Exon 2 of 8	NP_001192273.1	P13688-10
	CEACAM1	NM_001024912.3		c.369A>C	p.Gln123His	missense	Exon 2 of 8	NP_001020083.1	P13688-8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM1	ENST00000161559.11	TSL:1 MANE Select	c.369A>C	p.Gln123His	missense	Exon 2 of 9	ENSP00000161559.6	P13688-1
	CEACAM1	ENST00000403444.7	TSL:1	c.369A>C	p.Gln123His	missense	Exon 2 of 8	ENSP00000384709.3	P13688-8
	CEACAM1	ENST00000358394.7	TSL:1	c.369A>C	p.Gln123His	missense	Exon 2 of 9	ENSP00000351165.2	P13688-5

Frequencies

GnomAD3 genomes AF: 0.0960 AC: 14550 AN: 151634 Hom.: 1826 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00193

Gnomad OTH AF: 0.0764

GnomAD2 exomes AF: 0.0284 AC: 6858 AN: 241440 AF XY: 0.0211

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.0204

Gnomad ASJ exome AF: 0.00719

Gnomad EAS exome AF: 0.000326

Gnomad FIN exome AF: 0.00314

Gnomad NFE exome AF: 0.00396

Gnomad OTH exome AF: 0.0180

GnomAD4 exome AF: 0.0113 AC: 16151 AN: 1430628 Hom.: 1545 Cov.: 32 AF XY: 0.0100 AC XY: 7147 AN XY: 712180

African (AFR) AF: 0.351 AC: 11503 AN: 32800

American (AMR) AF: 0.0221 AC: 972 AN: 44070

Ashkenazi Jewish (ASJ) AF: 0.00495 AC: 127 AN: 25646

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

South Asian (SAS) AF: 0.00110 AC: 94 AN: 85750

European-Finnish (FIN) AF: 0.000649 AC: 34 AN: 52370

Middle Eastern (MID) AF: 0.0320 AC: 184 AN: 5750

European-Non Finnish (NFE) AF: 0.00150 AC: 1626 AN: 1085110

Other (OTH) AF: 0.0269 AC: 1599 AN: 59432

GnomAD4 genome AF: 0.0963 AC: 14611 AN: 151748 Hom.: 1838 Cov.: 32 AF XY: 0.0926 AC XY: 6871 AN XY: 74210

African (AFR) AF: 0.331 AC: 13585 AN: 41042

American (AMR) AF: 0.0447 AC: 683 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00193 AC: 131 AN: 68014

Other (OTH) AF: 0.0813 AC: 171 AN: 2104

Alfa AF: 0.0543 Hom.: 389

TwinsUK AF: 0.000809 AC: 3

ALSPAC AF: 0.00259 AC: 10

ESP6500AA AF: 0.340 AC: 1500

ESP6500EA AF: 0.00326 AC: 28

ExAC AF: 0.0401 AC: 4865

Asia WGS AF: 0.0530 AC: 183 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	6.5
DANN	Benign	0.64
DEOGEN2	Benign	0.13	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.024	T
MetaRNN	Benign	0.012	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.96
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.091
Sift	Benign	0.67	T
Sift4G	Benign	0.26	T
Polyphen		0.017	B
Vest4		0.047
MutPred		0.36		Gain of ubiquitination at K126 (P = 0.1008)
MPC		0.20
ClinPred		0.0066	T
GERP RS		-5.0
Varity_R		0.35
gMVP		0.57
Mutation Taster		=95/5	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: rs8111468; hg19: chr19-43031248; COSMIC: COSV50725617; COSMIC: COSV50725617;