1-151838529-G-A

Variant names:

• chr1-151838529-G-A
• rs1334687036
• NM_001394591.1:c.461C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001394591.1(C2CD4D):​c.461C>T​(p.Pro154Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000838 in 1,193,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. P154Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 8.4e-7 (0 hom.)
• Consequence: C2CD4D NM_001394591.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.48
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33646017).

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.461C>T	p.Pro154Leu	missense	Exon 2 of 2	NP_001381520.1	B7Z1M9
	C2CD4D	NM_001136003.2		c.461C>T	p.Pro154Leu	missense	Exon 2 of 2	NP_001129475.1	B7Z1M9
	C2CD4D	NM_001394592.1		c.461C>T	p.Pro154Leu	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.461C>T	p.Pro154Leu	missense	Exon 2 of 2	ENSP00000511551.1	B7Z1M9
	C2CD4D	ENST00000454109.1	TSL:2	c.461C>T	p.Pro154Leu	missense	Exon 2 of 2	ENSP00000389554.1	B7Z1M9
	C2CD4D	ENST00000694869.1		c.461C>T	p.Pro154Leu	missense	Exon 2 of 2	ENSP00000511552.1	B7Z1M9

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 8.38e-7 AC: 1 AN: 1193416 Hom.: 0 Cov.: 32 AF XY: 0.00000172 AC XY: 1 AN XY: 579916

African (AFR) AF: 0.00 AC: 0 AN: 23946

American (AMR) AF: 0.00 AC: 0 AN: 10836

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17166

East Asian (EAS) AF: 0.00 AC: 0 AN: 27000

South Asian (SAS) AF: 0.00 AC: 0 AN: 48434

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 28570

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3710

European-Non Finnish (NFE) AF: 0.00000102 AC: 1 AN: 985198

Other (OTH) AF: 0.00 AC: 0 AN: 48556

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.096	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.25	T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.47	T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.34	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.5
PrimateAI	Pathogenic	0.92	D
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.13
Sift	Benign	0.19	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.14
MutPred		0.20		Gain of MoRF binding (P = 0.0528)
MVP		0.51
ClinPred		0.97	D
GERP RS		3.5
Varity_R		0.17
gMVP		0.41
Mutation Taster		=77/23	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: rs1334687036; hg19: chr1-151811005;