rs56268318

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000293.3(PHKB):c.775-6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0522 in 1,607,860 control chromosomes in the GnomAD database, including 5,304 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 2299 hom., cov: 32)

Exomes 𝑓: 0.045 ( 3005 hom. )

Consequence

PHKB
NM_000293.3 splice_region, intron

Scores

Splicing: ADA: 0.000006794

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 1.61

Publications

4 publications found

Variant links:

Genes affected

PHKB (HGNC:8927): (phosphorylase kinase regulatory subunit beta) Phosphorylase kinase is a polymer of 16 subunits, four each of alpha, beta, gamma and delta. The alpha subunit includes the skeletal muscle and hepatic isoforms, encoded by two different genes. The beta subunit is the same in both the muscle and hepatic isoforms, encoded by this gene, which is a member of the phosphorylase b kinase regulatory subunit family. The gamma subunit also includes the skeletal muscle and hepatic isoforms, encoded by two different genes. The delta subunit is a calmodulin and can be encoded by three different genes. The gamma subunits contain the active site of the enzyme, whereas the alpha and beta subunits have regulatory functions controlled by phosphorylation. The delta subunit mediates the dependence of the enzyme on calcium concentration. Mutations in this gene cause glycogen storage disease type 9B, also known as phosphorylase kinase deficiency of liver and muscle. Alternatively spliced transcript variants encoding different isoforms have been identified in this gene. Two pseudogenes have been found on chromosomes 14 and 20, respectively.[provided by RefSeq, Feb 2010]

PHKB Gene-Disease associations (from GenCC):

glycogen storage disease IXb
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen

PHKB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 16-47587662-G-C is Benign according to our data. Variant chr16-47587662-G-C is described in ClinVar as Benign. ClinVar VariationId is 257179.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHKB	NM_000293.3	MANE Select	c.775-6G>C	splice_region intron	N/A	NP_000284.1	Q93100-1
PHKB	NM_001363837.1		c.775-6G>C	splice_region intron	N/A	NP_001350766.1	Q93100-3
PHKB	NM_001031835.3		c.754-6G>C	splice_region intron	N/A	NP_001027005.1	Q93100-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHKB	ENST00000323584.10	TSL:1 MANE Select	c.775-6G>C	splice_region intron	N/A	ENSP00000313504.5	Q93100-1
PHKB	ENST00000566044.5	TSL:1	c.754-6G>C	splice_region intron	N/A	ENSP00000456729.1	Q93100-4
PHKB	ENST00000567402.5	TSL:1	n.790-6G>C	splice_region intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17776

AN:

151912

Hom.:

2278

Cov.:

show subpopulations

Gnomad AFR

AF:

0.322

Gnomad AMI

AF:

0.00329

Gnomad AMR

AF:

0.0623

Gnomad ASJ

AF:

0.0317

Gnomad EAS

AF:

0.0137

Gnomad SAS

AF:

0.0291

Gnomad FIN

AF:

0.0183

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0412

Gnomad OTH

AF:

0.0982

GnomAD2 exomes

AF:

0.0524

AC:

13140

AN:

250894

AF XY:

0.0477

show subpopulations

Gnomad AFR exome

AF:

0.324

Gnomad AMR exome

AF:

0.0356

Gnomad ASJ exome

AF:

0.0299

Gnomad EAS exome

AF:

0.0141

Gnomad FIN exome

AF:

0.0163

Gnomad NFE exome

AF:

0.0410

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.0454

AC:

66063

AN:

1455830

Hom.:

3005

Cov.:

AF XY:

0.0440

AC XY:

31900

AN XY:

724696

show subpopulations

African (AFR)

AF:

0.324

AC:

10776

AN:

33288

American (AMR)

AF:

0.0389

AC:

1737

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.0306

AC:

798

AN:

26088

East Asian (EAS)

AF:

0.00772

AC:

306

AN:

39648

South Asian (SAS)

AF:

0.0267

AC:

2297

AN:

86110

European-Finnish (FIN)

AF:

0.0156

AC:

830

AN:

53304

Middle Eastern (MID)

AF:

0.0643

AC:

370

AN:

5758

European-Non Finnish (NFE)

AF:

0.0413

AC:

45668

AN:

1106820

Other (OTH)

AF:

0.0545

AC:

3281

AN:

60156

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

2556

5112

7667

10223

12779

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1832

3664

5496

7328

9160

<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:

0.117

AC:

17840

AN:

152030

Hom.:

2299

Cov.:

AF XY:

0.114

AC XY:

8457

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.322

AC:

13350

AN:

41424

American (AMR)

AF:

0.0621

AC:

948

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0317

AC:

110

AN:

3468

East Asian (EAS)

AF:

0.0135

AC:

AN:

5184

South Asian (SAS)

AF:

0.0285

AC:

137

AN:

4806

European-Finnish (FIN)

AF:

0.0183

AC:

193

AN:

10572

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0412

AC:

2802

AN:

67996

Other (OTH)

AF:

0.0981

AC:

207

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

670

1340

2011

2681

3351

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

172

344

516

688

860

<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:

0.0611

Hom.:

202

Bravo

AF:

0.129

Asia WGS

AF:

0.0390

AC:

137

AN:

3478

EpiCase

AF:

0.0480

EpiControl

AF:

0.0470

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Glycogen storage disease IXb (2)

not provided (2)

not specified (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.5

(source)

DANN

Benign

0.60

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=95/5

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0000068

dbscSNV1_RF

Benign

0.0080

Splicevardb

2.0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over