chr19-407434-G-T

Variant names:

• chr19-407434-G-T
• rs1178340779
• NM_001136263.2:c.928C>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001136263.2(C2CD4C):​c.928C>A​(p.Arg310Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000133 in 1,498,406 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.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: C2CD4C NM_001136263.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 0 publications found

Genes affected

C2CD4C (HGNC:29417): (C2 calcium dependent domain containing 4C) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=0.582 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136263.2. 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
	C2CD4C	NM_001136263.2	MANE Select	c.928C>A	p.Arg310Arg	synonymous	Exon 2 of 2	NP_001129735.1	Q8TF44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C2CD4C	ENST00000332235.8	TSL:2 MANE Select	c.928C>A	p.Arg310Arg	synonymous	Exon 2 of 2	ENSP00000328677.4	Q8TF44
	C2CD4C	ENST00000920287.1		c.928C>A	p.Arg310Arg	synonymous	Exon 2 of 2	ENSP00000590346.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151954 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

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

GnomAD2 exomes AF: 0.0000103 AC: 1 AN: 97038 AF XY: 0.0000191

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000274

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.43e-7 AC: 1 AN: 1346452 Hom.: 0 Cov.: 31 AF XY: 0.00000151 AC XY: 1 AN XY: 661540

African (AFR) AF: 0.00 AC: 0 AN: 30038

American (AMR) AF: 0.00 AC: 0 AN: 29962

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22378

East Asian (EAS) AF: 0.00 AC: 0 AN: 35012

South Asian (SAS) AF: 0.00 AC: 0 AN: 71990

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34256

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4670

European-Non Finnish (NFE) AF: 9.42e-7 AC: 1 AN: 1062078

Other (OTH) AF: 0.00 AC: 0 AN: 56068

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151954 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74212

African (AFR) AF: 0.0000242 AC: 1 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15266

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67932

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000366 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	6.8
DANN	Benign	0.87
PhyloP100		0.58

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: rs1178340779; hg19: chr19-407434;