dbSNP rs9844666: PCCB:c.184-482G>A (chr3-136255374-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000532.5(PCCB):c.184-482G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 205,002 control chromosomes in the GnomAD database, including 3,966 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 0.16 ( 2682 hom., cov: 32)

Exomes 𝑓: 0.20 ( 1284 hom. )

Consequence

PCCB
NM_000532.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.995

Publications

42 publications found

Variant links:

Genes affected

PCCB (HGNC:8654): (propionyl-CoA carboxylase subunit beta) The protein encoded by this gene is a subunit of the propionyl-CoA carboxylase (PCC) enzyme, which is involved in the catabolism of propionyl-CoA. PCC is a mitochondrial enzyme that probably acts as a dodecamer of six alpha subunits and six beta subunits. This gene encodes the beta subunit of PCC. Defects in this gene are a cause of propionic acidemia type II (PA-2). Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

PCCB Gene-Disease associations (from GenCC):

propionic acidemia
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Myriad Women’s Health, Orphanet

PCCB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PCCB	NM_000532.5 link	c.184-482G>A	intron_variant	Intron 1 of 14	ENST00000251654.9	NP_000523.2	P05166-1
PCCB	NM_001178014.2 link	c.184-482G>A	intron_variant	Intron 1 of 15		NP_001171485.1	P05166-2
PCCB	XM_011512873.2 link	c.184-482G>A	intron_variant	Intron 1 of 10		XP_011511175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PCCB	ENST00000251654.9 link	c.184-482G>A		intron_variant	Intron 1 of 14	1	NM_000532.5	ENSP00000251654.4		P05166-1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24786

AN:

151990

Hom.:

2683

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0403

Gnomad AMI

AF:

0.168

Gnomad AMR

AF:

0.135

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.00212

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.221

Gnomad MID

AF:

0.196

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.156

GnomAD4 exome

AF:

0.196

AC:

10392

AN:

52894

Hom.:

1284

Cov.:

AF XY:

0.201

AC XY:

5651

AN XY:

28110

show subpopulations

African (AFR)

AF:

0.0245

AC:

AN:

1304

American (AMR)

AF:

0.120

AC:

419

AN:

3506

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

195

AN:

1054

East Asian (EAS)

AF:

0.000357

AC:

AN:

2802

South Asian (SAS)

AF:

0.245

AC:

1760

AN:

7184

European-Finnish (FIN)

AF:

0.203

AC:

423

AN:

2082

Middle Eastern (MID)

AF:

0.187

AC:

AN:

150

European-Non Finnish (NFE)

AF:

0.219

AC:

7029

AN:

32166

Other (OTH)

AF:

0.191

AC:

505

AN:

2646

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

387

774

1160

1547

1934

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

192

256

320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.163

AC:

24772

AN:

152108

Hom.:

2682

Cov.:

AF XY:

0.162

AC XY:

12056

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0402

AC:

1672

AN:

41544

American (AMR)

AF:

0.134

AC:

2053

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

792

AN:

3472

East Asian (EAS)

AF:

0.00213

AC:

AN:

5170

South Asian (SAS)

AF:

0.229

AC:

1102

AN:

4810

European-Finnish (FIN)

AF:

0.221

AC:

2339

AN:

10574

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16266

AN:

67948

Other (OTH)

AF:

0.154

AC:

325

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1002

2005

3007

4010

5012

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

286

572

858

1144

1430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.213

Hom.:

17637

Bravo

AF:

0.149

Asia WGS

AF:

0.0900

AC:

314

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

9.0

(source)

DANN

Benign

0.54

PhyloP100

0.99

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over