chr19-41621742-C-G

Variant names:

• chr19-41621742-C-G
• rs782105663
• NM_001817.4:c.451G>C

Variant summary

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

The NM_001817.4(CEACAM4):​c.451G>C​(p.Gly151Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,459,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CEACAM4 NM_001817.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.16
• Publications: 2 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.451G>C	p.Gly151Arg	missense	Exon 3 of 7	NP_001808.2	O75871
	CEACAM4	NM_001362495.2		c.451G>C	p.Gly151Arg	missense	Exon 3 of 6	NP_001349424.1	A0A077JIU5
	CEACAM4	NM_001362493.2		c.91G>C	p.Gly31Arg	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.451G>C	p.Gly151Arg	missense	Exon 3 of 7	ENSP00000221954.2	O75871
	CEACAM4	ENST00000600925.1	TSL:2	c.451G>C	p.Gly151Arg	missense	Exon 3 of 6	ENSP00000473018.1	M0R363
	CEACAM4	ENST00000902906.1		c.91G>C	p.Gly31Arg	missense	Exon 2 of 6	ENSP00000572965.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249734 AF XY: 0.00000740

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1459862 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726378

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33446

American (AMR) AF: 0.0000224 AC: 1 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1110356

Other (OTH) AF: 0.00 AC: 0 AN: 60304

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000568638), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

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	Uncertain	0.34
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	19
DANN	Benign	0.87
DEOGEN2	Benign	0.034	T
Eigen	Benign	-0.011
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.070	N
M_CAP	Benign	0.0021	T
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.2
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-3.1	D
REVEL	Benign	0.056
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.61
MutPred		0.54		Loss of catalytic residue at V150 (P = 0.0648)
MVP		0.59
MPC		0.031
ClinPred		0.33	T
GERP RS		3.3
Varity_R		0.12
gMVP		0.55
Mutation Taster		=91/9	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: rs782105663; hg19: chr19-42128115;