rs2275116

Variant names:

• chr1-42463308-A-C
• rs2275116
• NM_001395517.1:c.-682A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-42463308-A-C
• chr1-42463308-A-G
• chr1-42463308-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395517.1(CCDC30):​c.-682A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 152,160 control chromosomes in the GnomAD database, including 13,010 homozygotes. 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 0.40 (13009 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: CCDC30 NM_001395517.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.73
• Publications: 2 publications found

Genes affected

CCDC30 (HGNC:26103): (coiled-coil domain containing 30)

PPCS (HGNC:25686): (phosphopantothenoylcysteine synthetase) Biosynthesis of coenzyme A (CoA) from pantothenic acid (vitamin B5) is an essential universal pathway in prokaryotes and eukaryotes. PPCS (EC 6.3.2.5), one of the last enzymes in this pathway, converts phosphopantothenate to phosphopantothenoylcysteine (Daugherty et al., 2002 [PubMed 11923312]).[supplied by OMIM, Mar 2008]

PPCS Gene-Disease associations (from GenCC):

• cardiomyopathy, dilated, 2c

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial isolated dilated cardiomyopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC30	NM_001395517.1	c.-682A>C		5_prime_UTR_variant	Exon 1 of 21	ENST00000657597.2	NP_001382446.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC30	ENST00000657597.2	c.-682A>C		5_prime_UTR_variant	Exon 1 of 21		NM_001395517.1	ENSP00000499662.2

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61238 AN: 152030 Hom.: 12984 Cov.: 33

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.401

GnomAD4 exome AF: 0.500 AC: 5 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.500 AC: 1 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 4 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.403 AC: 61314 AN: 152150 Hom.: 13009 Cov.: 33 AF XY: 0.402 AC XY: 29897 AN XY: 74392

African (AFR) AF: 0.492 AC: 20416 AN: 41518

American (AMR) AF: 0.346 AC: 5293 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1328 AN: 3468

East Asian (EAS) AF: 0.592 AC: 3043 AN: 5144

South Asian (SAS) AF: 0.532 AC: 2570 AN: 4828

European-Finnish (FIN) AF: 0.279 AC: 2961 AN: 10604

Middle Eastern (MID) AF: 0.391 AC: 115 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24423 AN: 67982

Other (OTH) AF: 0.406 AC: 858 AN: 2112

Alfa AF: 0.203 Hom.: 403

Bravo AF: 0.413

Asia WGS AF: 0.585 AC: 2035 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.66
DANN	Benign	0.29
PhyloP100		-1.7
PromoterAI		0.020	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2275116; hg19: chr1-42928979; COSMIC: COSV65333996;