15-62164273-C-T

Variant names:

• chr15-62164273-C-T
• rs1325603145
• NM_001007595.3:c.712G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001007595.3(C2CD4B):​c.712G>A​(p.Glu238Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000784 in 1,275,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. E238Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: C2CD4B NM_001007595.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646
• Publications: 0 publications found

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

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=0.07556203).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001007595.3. 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
	C2CD4B	NM_001007595.3	MANE Select	c.712G>A	p.Glu238Lys	missense	Exon 2 of 2	NP_001007596.2	A6NLJ0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD4B	ENST00000380392.4	TSL:2 MANE Select	c.712G>A	p.Glu238Lys	missense	Exon 2 of 2	ENSP00000369755.3	A6NLJ0
	C2CD4B	ENST00000948855.1		c.712G>A	p.Glu238Lys	missense	Exon 2 of 2	ENSP00000618914.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.84e-7 AC: 1 AN: 1275708 Hom.: 0 Cov.: 37 AF XY: 0.00000159 AC XY: 1 AN XY: 627114

African (AFR) AF: 0.00 AC: 0 AN: 25284

American (AMR) AF: 0.00 AC: 0 AN: 16722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20616

East Asian (EAS) AF: 0.00 AC: 0 AN: 28050

South Asian (SAS) AF: 0.00 AC: 0 AN: 64516

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31484

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3850

European-Non Finnish (NFE) AF: 9.69e-7 AC: 1 AN: 1032360

Other (OTH) AF: 0.00 AC: 0 AN: 52826

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.076	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		0.65
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.044
Sift	Benign	0.43	T
Sift4G	Benign	0.32	T
Polyphen		0.078	B
Vest4		0.13
MutPred		0.29		Gain of MoRF binding (P = 0.0037)
MVP		0.26
MPC		0.98
ClinPred		0.40	T
GERP RS		0.63
Varity_R		0.071
gMVP		0.20

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: rs1325603145; hg19: chr15-62456472;