19-41625637-C-G

Variant names:

• chr19-41625637-C-G
• rs200115429
• NM_001817.4:c.388G>C

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.388G>C​(p.Asp130His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,441,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 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. D130N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: CEACAM4 NM_001817.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• Publications: 1 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=0.089163184).

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.388G>C	p.Asp130His	missense	Exon 2 of 7	NP_001808.2	O75871
	CEACAM4	NM_001362495.2		c.388G>C	p.Asp130His	missense	Exon 2 of 6	NP_001349424.1	A0A077JIU5
	CEACAM4	NM_001362492.2		c.388G>C	p.Asp130His	missense	Exon 2 of 6	NP_001349421.1	A0A077JJN3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEACAM4	ENST00000221954.7	TSL:1 MANE Select	c.388G>C	p.Asp130His	missense	Exon 2 of 7	ENSP00000221954.2	O75871
	CEACAM4	ENST00000600925.1	TSL:2	c.388G>C	p.Asp130His	missense	Exon 2 of 6	ENSP00000473018.1	M0R363
	CEACAM4	ENST00000902906.1		c.64+1263G>C		intron	N/A	ENSP00000572965.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000424 AC: 1 AN: 235786 AF XY: 0.00000789

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1441650 Hom.: 0 Cov.: 33 AF XY: 0.00000280 AC XY: 2 AN XY: 714944

African (AFR) AF: 0.00 AC: 0 AN: 33070

American (AMR) AF: 0.00 AC: 0 AN: 43526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24364

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.0000242 AC: 2 AN: 82776

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52512

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5652

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100638

Other (OTH) AF: 0.00 AC: 0 AN: 59556

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.2
DANN	Benign	0.94
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0023	N
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.5
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.88	N
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.12
MutPred		0.24		Gain of loop (P = 0.1069)
MVP		0.22
MPC		0.040
ClinPred		0.28	T
GERP RS		-3.6
Varity_R		0.13
gMVP		0.19
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs200115429; hg19: chr19-42132011;