rs372913381

Variant names:

• chr19-41625631-C-G
• NM_001817.4:c.394G>C

Your query was ambiguous. Multiple possible variants found:

• chr19-41625631-C-G
• chr19-41625631-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001817.4(CEACAM4):​c.394G>C​(p.Asp132His) 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 1,436,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. D132N) 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: -0.612

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=0.10868999).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEACAM4	NM_001817.4	c.394G>C	p.Asp132His	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.394G>C	p.Asp132His	missense_variant	Exon 2 of 7	1	NM_001817.4	ENSP00000221954.2
CEACAM4	ENST00000600925.1	c.394G>C	p.Asp132His	missense_variant	Exon 2 of 6	2		ENSP00000473018.1
CEACAM4	ENST00000472081.1	n.505G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1436088 Hom.: 0 Cov.: 33 AF XY: 0.00000141 AC XY: 1 AN XY: 711376

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: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000182

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T;.
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.0099	N
M_CAP	Benign	0.0044	T
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.4	N;.
REVEL	Benign	0.10
Sift	Uncertain	0.010	D;.
Sift4G	Uncertain	0.022	D;D
Polyphen		0.98	D;.
Vest4		0.14
MutPred		0.36		Gain of disorder (P = 0.0977);Gain of disorder (P = 0.0977);
MVP		0.27
MPC		0.040
ClinPred		0.24	T
GERP RS		-0.62
Varity_R		0.11
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-42132005;