chr6-31668965-A-G

Variant names:

• chr6-31668965-A-G
• rs9267531
• NM_001320.7:c.292-132A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001320.7(CSNK2B):​c.292-132A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 675,906 control chromosomes in the GnomAD database, including 2,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.073 (536 hom., cov: 32)
  • Exomes 𝑓: 0.079 (2463 hom.)
• Consequence: CSNK2B NM_001320.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.23
• Publications: 41 publications found

Genes affected

CSNK2B (HGNC:2460): (casein kinase 2 beta) This gene encodes the beta subunit of casein kinase II, a ubiquitous protein kinase which regulates metabolic pathways, signal transduction, transcription, translation, and replication. The enzyme is composed of three subunits, alpha, alpha prime and beta, which form a tetrameric holoenzyme. The alpha and alpha prime subunits are catalytic, while the beta subunit serves regulatory functions. The enzyme localizes to the endoplasmic reticulum and the Golgi apparatus. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2013]

CSNK2B Gene-Disease associations (from GenCC):

• Poirier-Bienvenu neurodevelopmental syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, ClinGen, Illumina, Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000263020 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-31668965-A-G is Benign according to our data. Variant chr6-31668965-A-G is described in ClinVar as Benign. ClinVar VariationId is 1182177.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.106 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320.7. 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
	CSNK2B	NM_001320.7	MANE Select	c.292-132A>G		intron	N/A	NP_001311.3
	CSNK2B	NM_001282385.2		c.292-132A>G		intron	N/A	NP_001269314.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2B	ENST00000375882.7	TSL:1 MANE Select	c.292-132A>G		intron	N/A	ENSP00000365042.3
	ENSG00000263020	ENST00000617558.2	TSL:1	c.292-132A>G		intron	N/A	ENSP00000483989.2
	ENSG00000263020	ENST00000375880.6	TSL:3	c.292-132A>G		intron	N/A	ENSP00000365040.2

Frequencies

GnomAD3 genomes AF: 0.0731 AC: 11122 AN: 152156 Hom.: 536 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.0691

Gnomad AMR AF: 0.0354

Gnomad ASJ AF: 0.0398

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.0789

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.0560

GnomAD4 exome AF: 0.0791 AC: 41426 AN: 523632 Hom.: 2463 Cov.: 6 AF XY: 0.0755 AC XY: 20851 AN XY: 276028

African (AFR) AF: 0.0525 AC: 744 AN: 14174

American (AMR) AF: 0.0264 AC: 634 AN: 23990

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 636 AN: 15104

East Asian (EAS) AF: 0.0000620 AC: 2 AN: 32258

South Asian (SAS) AF: 0.00264 AC: 137 AN: 51936

European-Finnish (FIN) AF: 0.0813 AC: 3383 AN: 41626

Middle Eastern (MID) AF: 0.00765 AC: 21 AN: 2744

European-Non Finnish (NFE) AF: 0.107 AC: 33635 AN: 313272

Other (OTH) AF: 0.0783 AC: 2234 AN: 28528

GnomAD4 genome AF: 0.0730 AC: 11122 AN: 152274 Hom.: 536 Cov.: 32 AF XY: 0.0681 AC XY: 5074 AN XY: 74458

African (AFR) AF: 0.0503 AC: 2090 AN: 41552

American (AMR) AF: 0.0353 AC: 540 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0398 AC: 138 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4830

European-Finnish (FIN) AF: 0.0789 AC: 837 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7323 AN: 68002

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.106 Hom.: 2847

Bravo AF: 0.0694

Asia WGS AF: 0.00837 AC: 30 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.031
DANN	Benign	0.61
PhyloP100		-2.2
PromoterAI		-0.0060	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs9267531; hg19: chr6-31636742;