19-42583272-C-T

Variant names:

• chr19-42583272-C-T
• NM_001816.4:c.1024G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001816.4(CEACAM8):​c.1024G>A​(p.Val342Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CEACAM8 NM_001816.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.316

Genes affected

CEACAM8 (HGNC:1820): (CEA cell adhesion molecule 8) Enables protein heterodimerization activity. Involved in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules. Located in cell surface and extracellular space. Biomarker of severe acute respiratory syndrome. [provided by Alliance of Genome Resources, Apr 2022]

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

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07195753).
• BP6: Variant 19-42583272-C-T is Benign according to our data. Variant chr19-42583272-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2247778.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM8	NM_001816.4	c.1024G>A	p.Val342Ile	missense_variant	Exon 5 of 6	ENST00000244336.10	NP_001807.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM8	ENST00000244336.10	c.1024G>A	p.Val342Ile	missense_variant	Exon 5 of 6	1	NM_001816.4	ENSP00000244336.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Sep 01, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.76
DANN	Benign	0.33
DEOGEN2	Benign	0.034	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0097	N
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.00087	T
MetaRNN	Benign	0.072	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.15	N;.
REVEL	Benign	0.026
Sift	Benign	0.32	T;.
Sift4G	Benign	0.13	T;T
Polyphen		0.0030	B;.
Vest4		0.047
MutPred		0.48		Loss of catalytic residue at V342 (P = 0.0395);.;
MVP		0.18
MPC		0.017
ClinPred		0.053	T
GERP RS		0.60
Varity_R		0.025
gMVP		0.20

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-43087424;