1-151838640-C-T

Variant names:

• chr1-151838640-C-T
• rs1407577580
• NM_001394591.1:c.350G>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.350G>A​(p.Gly117Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000676 in 1,331,252 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. G117V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000068 (0 hom.)
• Consequence: C2CD4D NM_001394591.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.520
• 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=0.092724174).

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.350G>A	p.Gly117Glu	missense	Exon 2 of 2	NP_001381520.1	B7Z1M9
	C2CD4D	NM_001136003.2		c.350G>A	p.Gly117Glu	missense	Exon 2 of 2	NP_001129475.1	B7Z1M9
	C2CD4D	NM_001394592.1		c.350G>A	p.Gly117Glu	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.350G>A	p.Gly117Glu	missense	Exon 2 of 2	ENSP00000511551.1	B7Z1M9
	C2CD4D	ENST00000454109.1	TSL:2	c.350G>A	p.Gly117Glu	missense	Exon 2 of 2	ENSP00000389554.1	B7Z1M9
	C2CD4D	ENST00000694869.1		c.350G>A	p.Gly117Glu	missense	Exon 2 of 2	ENSP00000511552.1	B7Z1M9

Frequencies

GnomAD3 genomes AF: 0.00000661 AC: 1 AN: 151370 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

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: 0.00000678 AC: 8 AN: 1179882 Hom.: 0 Cov.: 32 AF XY: 0.00000700 AC XY: 4 AN XY: 571292

African (AFR) AF: 0.00 AC: 0 AN: 23686

American (AMR) AF: 0.00 AC: 0 AN: 11302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16750

East Asian (EAS) AF: 0.000187 AC: 5 AN: 26754

South Asian (SAS) AF: 0.00 AC: 0 AN: 45086

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27342

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3286

European-Non Finnish (NFE) AF: 0.00000205 AC: 2 AN: 977612

Other (OTH) AF: 0.0000208 AC: 1 AN: 48064

GnomAD4 genome AF: 0.00000661 AC: 1 AN: 151370 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73926

African (AFR) AF: 0.00 AC: 0 AN: 41254

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

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5102

South Asian (SAS) AF: 0.00 AC: 0 AN: 4808

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10466

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 310

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67762

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

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	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	14
DANN	Benign	0.92
DEOGEN2	Benign	0.014	T
Eigen	Benign	-0.92
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0088	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		0.52
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.87	N
REVEL	Benign	0.023
Sift	Benign	0.24	T
Sift4G	Benign	0.15	T
Polyphen		0.024	B
Vest4		0.22
MutPred		0.14		Loss of glycosylation at P112 (P = 0.1882)
MVP		0.22
ClinPred		0.089	T
GERP RS		1.6
Varity_R		0.040
gMVP		0.16
Mutation Taster		=89/11	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: rs1407577580; hg19: chr1-151811116;