rs8111468

chr19-42527096-T-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.011648744).
• BP6: Variant 19-42527096-T-G is Benign according to our data. Variant chr19-42527096-T-G is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CEACAM1	NM_001712.5	c.369A>C	p.Gln123His	missense_variant	2/9	ENST00000161559.11
LIPE-AS1	NR_073180.1	n.205+41873T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CEACAM1	ENST00000161559.11	c.369A>C	p.Gln123His	missense_variant	2/9	1	NM_001712.5	P2
LIPE-AS1	ENST00000594624.7	n.194+41873T>G		intron_variant, non_coding_transcript_variant		1

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

GnomAD3 exomes AF: 0.0284 AC: 6858 AN: 241440 Hom.: 698 AF XY: 0.0211 AC XY: 2754 AN XY: 130316

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 SAS exome AF: 0.00123

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

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.0221

Gnomad4 ASJ exome AF: 0.00495

Gnomad4 EAS exome AF: 0.000302

Gnomad4 SAS exome AF: 0.00110

Gnomad4 FIN exome AF: 0.000649

Gnomad4 NFE exome AF: 0.00150

Gnomad4 OTH exome AF: 0.0269

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

Gnomad4 AFR AF: 0.331

Gnomad4 AMR AF: 0.0447

Gnomad4 ASJ AF: 0.00605

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.0813

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 v4.3

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.024	T;T;T;T;T;T;T;T
MetaRNN	Benign	0.012	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L;L;L;L;L;.;.
MutationTaster	Benign	1.0	P;P;P;P;P;P;P;P;P;P
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-2.3	N;D;N;N;D;.;.;.
REVEL	Benign	0.091
Sift	Benign	0.67	T;T;T;T;T;.;.;.
Sift4G	Benign	0.26	T;T;T;T;T;T;T;.
Polyphen		0.017	B;B;B;B;B;.;.;.
Vest4		0.047
MutPred		0.36		Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);Gain of ubiquitination at K126 (P = 0.1008);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

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: rs8111468; hg19: chr19-43031248; COSMIC: COSV50725617; COSMIC: COSV50725617;