19-42522107-T-A

Variant names:

• chr19-42522107-T-A
• rs1314961085
• NM_001712.5:c.520A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001712.5(CEACAM1):​c.520A>T​(p.Thr174Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T174A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CEACAM1 NM_001712.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15516436).

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.520A>T	p.Thr174Ser	missense	Exon 3 of 9	NP_001703.2
	CEACAM1	NM_001205344.2		c.520A>T	p.Thr174Ser	missense	Exon 3 of 8	NP_001192273.1	P13688-10
	CEACAM1	NM_001024912.3		c.520A>T	p.Thr174Ser	missense	Exon 3 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.520A>T	p.Thr174Ser	missense	Exon 3 of 9	ENSP00000161559.6	P13688-1
	CEACAM1	ENST00000403444.7	TSL:1	c.520A>T	p.Thr174Ser	missense	Exon 3 of 8	ENSP00000384709.3	P13688-8
	CEACAM1	ENST00000358394.7	TSL:1	c.520A>T	p.Thr174Ser	missense	Exon 3 of 9	ENSP00000351165.2	P13688-5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461894 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

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

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1112012

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.040	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.11
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.021
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.18	T
Polyphen		0.52	P
Vest4		0.22
MutPred		0.51		Gain of loop (P = 0.1069)
MVP		0.17
MPC		0.61
ClinPred		0.40	T
GERP RS		-0.029
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.38
Mutation Taster		=81/19	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: rs1314961085; hg19: chr19-43026259;