19-41625919-A-G

Variant names:

• chr19-41625919-A-G
• rs944768185
• NM_001817.4:c.106T>C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001817.4(CEACAM4):​c.106T>C​(p.Phe36Leu) 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: CEACAM4 NM_001817.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.04

Genes affected

CEACAM4 (HGNC:1816): (CEA cell adhesion molecule 4) Involved in phagocytosis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.024371296).
• BP6: Variant 19-41625919-A-G is Benign according to our data. Variant chr19-41625919-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3489871.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM4	NM_001817.4	c.106T>C	p.Phe36Leu	missense_variant	Exon 2 of 7	ENST00000221954.7	NP_001808.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEACAM4	ENST00000221954.7	c.106T>C	p.Phe36Leu	missense_variant	Exon 2 of 7	1	NM_001817.4	ENSP00000221954.2
CEACAM4	ENST00000600925.1	c.106T>C	p.Phe36Leu	missense_variant	Exon 2 of 6	2		ENSP00000473018.1
CEACAM4	ENST00000472081.1	n.217T>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jul 30, 2024

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	Pathogenic	0.66
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.011
DANN	Benign	0.27
DEOGEN2	Benign	0.0024	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00053	N
M_CAP	Benign	0.00084	T
MetaRNN	Benign	0.024	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-1.0	N;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	2.5	N;.
REVEL	Benign	0.020
Sift	Benign	0.60	T;.
Sift4G	Benign	1.0	T;T
Polyphen		0.013	B;.
Vest4		0.025
MutPred		0.44		Loss of catalytic residue at F36 (P = 0.0385);Loss of catalytic residue at F36 (P = 0.0385);
MVP		0.055
MPC		0.028
ClinPred		0.057	T
GERP RS		-0.87
Varity_R		0.035
gMVP		0.061

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs944768185; hg19: chr19-42132293;