15-62164395-G-T

Variant names:

• chr15-62164395-G-T
• rs1441819524
• NM_001007595.3:c.590C>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.590C>A​(p.Ala197Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 151,880 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. A197V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C2CD4B NM_001007595.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.20
• 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=0.10132831).

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.590C>A	p.Ala197Asp	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.590C>A	p.Ala197Asp	missense	Exon 2 of 2	ENSP00000369755.3	A6NLJ0
	C2CD4B	ENST00000948855.1		c.590C>A	p.Ala197Asp	missense	Exon 2 of 2	ENSP00000618914.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1268676 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 622704

African (AFR) AF: 0.00 AC: 0 AN: 25444

American (AMR) AF: 0.00 AC: 0 AN: 18928

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20954

East Asian (EAS) AF: 0.00 AC: 0 AN: 27656

South Asian (SAS) AF: 0.00 AC: 0 AN: 63178

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31164

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3720

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1025280

Other (OTH) AF: 0.00 AC: 0 AN: 52352

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151880 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74250

African (AFR) AF: 0.0000241 AC: 1 AN: 41514

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67860

Other (OTH) AF: 0.00 AC: 0 AN: 2112

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Uncertain	0.98
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.24	N
LIST_S2	Benign	0.30	T
M_CAP	Uncertain	0.089	D
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.2
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.070
Sift	Benign	0.093	T
Sift4G	Benign	0.090	T
Polyphen		0.043	B
Vest4		0.11
MutPred		0.26		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.20
MPC		1.6
ClinPred		0.24	T
GERP RS		-0.34
Varity_R		0.23
gMVP		0.17

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: rs1441819524; hg19: chr15-62456594;