NM_001817.4:c.499G>A

Variant names:

• chr19-41621694-C-T
• rs1555801617
• NM_001817.4:c.499G>A

Variant summary

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

The NM_001817.4(CEACAM4):​c.499G>A​(p.Val167Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,460,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CEACAM4 NM_001817.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.16
• Publications: 0 publications found

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

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=0.07665223).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001817.4. 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
	CEACAM4	NM_001817.4	MANE Select	c.499G>A	p.Val167Met	missense	Exon 3 of 7	NP_001808.2	O75871
	CEACAM4	NM_001362495.2		c.499G>A	p.Val167Met	missense	Exon 3 of 6	NP_001349424.1	A0A077JIU5
	CEACAM4	NM_001362493.2		c.139G>A	p.Val47Met	missense	Exon 2 of 6	NP_001349422.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM4	ENST00000221954.7	TSL:1 MANE Select	c.499G>A	p.Val167Met	missense	Exon 3 of 7	ENSP00000221954.2	O75871
	CEACAM4	ENST00000600925.1	TSL:2	c.499G>A	p.Val167Met	missense	Exon 3 of 6	ENSP00000473018.1	M0R363
	CEACAM4	ENST00000902906.1		c.139G>A	p.Val47Met	missense	Exon 2 of 6	ENSP00000572965.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1460094 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 726520

African (AFR) AF: 0.0000299 AC: 1 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26110

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86218

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1110426

Other (OTH) AF: 0.00 AC: 0 AN: 60330

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.2
DANN	Benign	0.83
DEOGEN2	Benign	0.0051	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0011	N
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L
PhyloP100		-1.2
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.012
Sift	Benign	0.15	T
Sift4G	Benign	0.18	T
Polyphen		0.047	B
Vest4		0.12
MutPred		0.45		Loss of catalytic residue at V167 (P = 0.0145)
MVP		0.040
MPC		0.14
ClinPred		0.060	T
GERP RS		-6.6
Varity_R		0.023
gMVP		0.22
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1555801617; hg19: chr19-42128067;