19-41625637-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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. 16/21 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

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.089163184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM4	NM_001817.4	c.388G>C	p.Asp130His	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.388G>C	p.Asp130His	missense_variant	Exon 2 of 7	1	NM_001817.4	ENSP00000221954.2
CEACAM4	ENST00000600925.1	c.388G>C	p.Asp130His	missense_variant	Exon 2 of 6	2		ENSP00000473018.1
CEACAM4	ENST00000472081.1	n.499G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000424 AC: 1 AN: 235786 Hom.: 0 AF XY: 0.00000789 AC XY: 1 AN XY: 126666

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 SAS exome AF: 0.0000370

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000242

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.88	N;.
REVEL	Benign	0.12
Sift	Benign	0.12	T;.
Sift4G	Benign	0.18	T;T
Polyphen		1.0	D;.
Vest4		0.12
MutPred		0.24		Gain of loop (P = 0.1069);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

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: rs200115429; hg19: chr19-42132011;