rs3830242

Variant names:

• chr16-47650775-TATTA-T
• rs3830242
• NM_000293.3:c.1881-52_1881-49delAATT

Your query was ambiguous. Multiple possible variants found:

• chr16-47650775-TATTA-T
• chr16-47650775-TATTA-TATTAATTA

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000293.3(PHKB):​c.1881-52_1881-49delAATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,394,238 control chromosomes in the GnomAD database, including 133,750 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11734 hom., cov: 0)
  • Exomes 𝑓: 0.43 (122016 hom.)
• Consequence: PHKB NM_000293.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.435
• Publications: 1 publications found

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, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 16-47650775-TATTA-T is Benign according to our data. Variant chr16-47650775-TATTA-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 257173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.7 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHKB	NM_000293.3	c.1881-52_1881-49delAATT		intron_variant	Intron 19 of 30	ENST00000323584.10	NP_000284.1
PHKB	NM_001363837.1	c.1881-52_1881-49delAATT		intron_variant	Intron 19 of 30		NP_001350766.1
PHKB	NM_001031835.3	c.1860-52_1860-49delAATT		intron_variant	Intron 20 of 31		NP_001027005.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHKB	ENST00000323584.10	c.1881-55_1881-52delATTA		intron_variant	Intron 19 of 30	1	NM_000293.3	ENSP00000313504.5

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55930 AN: 151558 Hom.: 11736 Cov.: 0

Gnomad AFR AF: 0.174

Gnomad AMI AF: 0.533

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.411

Gnomad OTH AF: 0.389

GnomAD4 exome AF: 0.434 AC: 539108 AN: 1242560 Hom.: 122016 AF XY: 0.436 AC XY: 274562 AN XY: 629888

African (AFR) AF: 0.171 AC: 5005 AN: 29214

American (AMR) AF: 0.622 AC: 27611 AN: 44384

Ashkenazi Jewish (ASJ) AF: 0.413 AC: 10238 AN: 24780

East Asian (EAS) AF: 0.752 AC: 29067 AN: 38652

South Asian (SAS) AF: 0.499 AC: 40858 AN: 81804

European-Finnish (FIN) AF: 0.413 AC: 21455 AN: 51944

Middle Eastern (MID) AF: 0.399 AC: 2129 AN: 5336

European-Non Finnish (NFE) AF: 0.416 AC: 379748 AN: 913250

Other (OTH) AF: 0.432 AC: 22997 AN: 53196

GnomAD4 genome AF: 0.369 AC: 55946 AN: 151678 Hom.: 11734 Cov.: 0 AF XY: 0.375 AC XY: 27789 AN XY: 74092

African (AFR) AF: 0.173 AC: 7192 AN: 41468

American (AMR) AF: 0.499 AC: 7591 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.427 AC: 1475 AN: 3456

East Asian (EAS) AF: 0.719 AC: 3683 AN: 5120

South Asian (SAS) AF: 0.515 AC: 2481 AN: 4814

European-Finnish (FIN) AF: 0.405 AC: 4253 AN: 10498

Middle Eastern (MID) AF: 0.363 AC: 106 AN: 292

European-Non Finnish (NFE) AF: 0.411 AC: 27868 AN: 67820

Other (OTH) AF: 0.389 AC: 816 AN: 2096

Alfa AF: 0.368 Hom.: 1353

Bravo AF: 0.372

Asia WGS AF: 0.575 AC: 1997 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 31, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.43
Mutation Taster		=100/0	polymorphism (auto)

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: rs3830242; hg19: chr16-47684686;