chr1-151838436-C-T

Variant names:

• chr1-151838436-C-T
• rs1318643119
• NM_001394591.1:c.554G>A

Variant summary

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

The NM_001394591.1(C2CD4D):​c.554G>A​(p.Arg185His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000183 in 1,418,732 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R185S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000018 (1 hom.)
• Consequence: C2CD4D NM_001394591.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.84
• Publications: 0 publications found

Genes affected

C2CD4D (HGNC:37210): (C2 calcium dependent domain containing 4D)

C2CD4D-AS1 (HGNC:54045): (C2CD4D and THEM5 antisense RNA 1)

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=0.20082328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394591.1. 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
	C2CD4D	NM_001394591.1	MANE Select	c.554G>A	p.Arg185His	missense	Exon 2 of 2	NP_001381520.1	B7Z1M9
	C2CD4D	NM_001136003.2		c.554G>A	p.Arg185His	missense	Exon 2 of 2	NP_001129475.1	B7Z1M9
	C2CD4D	NM_001394592.1		c.554G>A	p.Arg185His	missense	Exon 2 of 2	NP_001381521.1	B7Z1M9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD4D	ENST00000694868.1	MANE Select	c.554G>A	p.Arg185His	missense	Exon 2 of 2	ENSP00000511551.1	B7Z1M9
	C2CD4D	ENST00000454109.1	TSL:2	c.554G>A	p.Arg185His	missense	Exon 2 of 2	ENSP00000389554.1	B7Z1M9
	C2CD4D	ENST00000694869.1		c.554G>A	p.Arg185His	missense	Exon 2 of 2	ENSP00000511552.1	B7Z1M9

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151540 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000726

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000182 AC: 23 AN: 1267192 Hom.: 1 Cov.: 32 AF XY: 0.0000161 AC XY: 10 AN XY: 622674

African (AFR) AF: 0.00 AC: 0 AN: 25322

American (AMR) AF: 0.00 AC: 0 AN: 18212

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20654

East Asian (EAS) AF: 0.00 AC: 0 AN: 27482

South Asian (SAS) AF: 0.00 AC: 0 AN: 63220

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4860

European-Non Finnish (NFE) AF: 0.0000225 AC: 23 AN: 1021828

Other (OTH) AF: 0.00 AC: 0 AN: 52146

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151540 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 74030

African (AFR) AF: 0.0000726 AC: 3 AN: 41314

American (AMR) AF: 0.00 AC: 0 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10450

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67808

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.57	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		1.8
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.093
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.67	P
Vest4		0.069
MutPred		0.21		Loss of methylation at R185 (P = 0.0516)
MVP		0.095
ClinPred		0.78	D
GERP RS		1.9
Varity_R		0.13
gMVP		0.28
Mutation Taster		=86/14	polymorphism

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: rs1318643119; hg19: chr1-151810912;