6-31666416-A-G

Variant names:

• chr6-31666416-A-G
• rs805257
• NM_001320.7:c.-12+208A>G

Variant summary

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

The NM_001320.7(CSNK2B):​c.-12+208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 186,002 control chromosomes in the GnomAD database, including 18,415 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 0.45 (16150 hom., cov: 31)
  • Exomes 𝑓: 0.35 (2265 hom.)
• Consequence: CSNK2B NM_001320.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.834
• Publications: 34 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]

ENSG00000263020 (HGNC:):

GPANK1 (HGNC:13920): (G-patch domain and ankyrin repeats 1) This gene is located in a cluster of HLA-B-associated transcripts, which is included in the human major histocompatability complex III region. This gene encodes a protein which is thought to play a role in immunity. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.591 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2B	NM_001320.7	MANE Select	c.-12+208A>G		intron	N/A	NP_001311.3
	CSNK2B	NM_001282385.2		c.-12+208A>G		intron	N/A	NP_001269314.1
	GPANK1	NM_001199237.1		c.-818T>C		upstream_gene	N/A	NP_001186166.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CSNK2B	ENST00000375882.7	TSL:1 MANE Select	c.-12+208A>G		intron	N/A	ENSP00000365042.3
	ENSG00000263020	ENST00000375880.6	TSL:3	c.-12+208A>G		intron	N/A	ENSP00000365040.2
	CSNK2B	ENST00000465481.6	TSL:1	n.122+208A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68540 AN: 151866 Hom.: 16128 Cov.: 31

Gnomad AFR AF: 0.597

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.496

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.443

GnomAD4 exome AF: 0.345 AC: 11738 AN: 34018 Hom.: 2265 Cov.: 4 AF XY: 0.347 AC XY: 6300 AN XY: 18144

African (AFR) AF: 0.597 AC: 437 AN: 732

American (AMR) AF: 0.380 AC: 901 AN: 2374

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 296 AN: 902

East Asian (EAS) AF: 0.379 AC: 604 AN: 1592

South Asian (SAS) AF: 0.331 AC: 1188 AN: 3590

European-Finnish (FIN) AF: 0.434 AC: 406 AN: 936

Middle Eastern (MID) AF: 0.357 AC: 40 AN: 112

European-Non Finnish (NFE) AF: 0.330 AC: 7258 AN: 21982

Other (OTH) AF: 0.338 AC: 608 AN: 1798

GnomAD4 genome AF: 0.451 AC: 68607 AN: 151984 Hom.: 16150 Cov.: 31 AF XY: 0.454 AC XY: 33736 AN XY: 74298

African (AFR) AF: 0.597 AC: 24731 AN: 41436

American (AMR) AF: 0.429 AC: 6545 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1167 AN: 3468

East Asian (EAS) AF: 0.399 AC: 2059 AN: 5166

South Asian (SAS) AF: 0.400 AC: 1930 AN: 4824

European-Finnish (FIN) AF: 0.496 AC: 5235 AN: 10546

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.376 AC: 25572 AN: 67968

Other (OTH) AF: 0.446 AC: 943 AN: 2112

Alfa AF: 0.404 Hom.: 47604

Bravo AF: 0.454

Asia WGS AF: 0.477 AC: 1655 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		-0.83
PromoterAI		-0.010	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs805257; hg19: chr6-31634193;