15-62164395-G-A

Variant names:

• chr15-62164395-G-A
• rs1441819524
• NM_001007595.3:c.590C>T

Variant summary

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

The NM_001007595.3(C2CD4B):​c.590C>T​(p.Ala197Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000394 in 1,268,676 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000039 (0 hom.)
• Consequence: C2CD4B NM_001007595.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.20

Genes affected

C2CD4B (HGNC:33628): (C2 calcium dependent domain containing 4B) Involved in positive regulation of acute inflammatory response; regulation of cell adhesion; and regulation of vascular permeability involved in acute inflammatory response. [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=0.09764704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C2CD4B	NM_001007595.3	c.590C>T	p.Ala197Val	missense_variant	Exon 2 of 2	ENST00000380392.4	NP_001007596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C2CD4B	ENST00000380392.4	c.590C>T	p.Ala197Val	missense_variant	Exon 2 of 2	2	NM_001007595.3	ENSP00000369755.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000394 AC: 5 AN: 1268676 Hom.: 0 Cov.: 35 AF XY: 0.00000482 AC XY: 3 AN XY: 622704

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: 0.00000488

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 09, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.590C>T (p.A197V) alteration is located in exon 2 (coding exon 1) of the C2CD4B gene. This alteration results from a C to T substitution at nucleotide position 590, causing the alanine (A) at amino acid position 197 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	9.5
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	-0.74
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.071	D
MetaRNN	Benign	0.098	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.046
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.031	D
Polyphen		0.077	B
Vest4		0.052
MutPred		0.34		Gain of sheet (P = 0.0149);
MVP		0.20
MPC		0.84
ClinPred		0.20	T
GERP RS		-0.34
Varity_R		0.066
gMVP		0.12

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

Publications

LitVar

Other links and lift over

dbSNP: rs1441819524; hg19: chr15-62456594;