22-50583192-C-CCGGCGGGG

Variant names:

• chr22-50583192-C-CCGGCGGGG
• rs538199922
• ENST00000380711.3:n.182_189dupGGCGGCGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000380711.3(CHKB-DT):​n.182_189dupGGCGGCGG variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0305 in 176,082 control chromosomes in the GnomAD database, including 297 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (296 hom., cov: 32)
  • Exomes 𝑓: 0.0017 (1 hom.)
• Consequence: CHKB-DT ENST00000380711.3 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.251

Genes affected

CHKB-DT (HGNC:40146): (CHKB divergent transcript)

CHKB (HGNC:1938): (choline kinase beta) Choline kinase (CK) and ethanolamine kinase (EK) catalyze the phosphorylation of choline/ethanolamine to phosphocholine/phosphoethanolamine. This is the first enzyme in the biosynthesis of phosphatidylcholine/phosphatidylethanolamine in all animal cells. The highly purified CKs from mammalian sources and their recombinant gene products have been shown to have EK activity also, indicating that both activities reside on the same protein. The choline kinase-like protein encoded by CHKL belongs to the choline/ethanolamine kinase family; however, its exact function is not known. Read-through transcripts are expressed from this locus that include exons from the downstream CPT1B locus. [provided by RefSeq, Jun 2009]

CHKB-CPT1B (HGNC:41998): (CHKB-CPT1B readthrough (NMD candidate)) The genes CHKB and CPT1B are adjacent on chromosome 22 and read-through transcripts are expressed that include exons from both loci. The read-through transcripts are candidates for nonsense-mediated mRNA decay (NMD) and are unlikely to express proteins. [provided by RefSeq, Jun 2009]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 22-50583192-C-CCGGCGGGG is Benign according to our data. Variant chr22-50583192-C-CCGGCGGGG is described in ClinVar as [Benign]. Clinvar id is 1259647.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHKB-DT	NR_021492.2	n.182_189dupGGCGGCGG		non_coding_transcript_exon_variant	Exon 1 of 2
CHKB-DT	NR_110536.1	n.182_189dupGGCGGCGG		non_coding_transcript_exon_variant	Exon 1 of 4
CHKB-CPT1B	NR_027928.2	n.-201_-194dupCCCCGCCG		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHKB-DT	ENST00000380711.3	n.182_189dupGGCGGCGG		non_coding_transcript_exon_variant	Exon 1 of 2	2
CHKB-DT	ENST00000648558.1	n.52_59dupGGCGGCGG		non_coding_transcript_exon_variant	Exon 1 of 4
CHKB-DT	ENST00000656328.1	n.88_95dupGGCGGCGG		non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.0349 AC: 5313 AN: 152070 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00433

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.00140

Gnomad OTH AF: 0.0287

GnomAD4 exome AF: 0.00167 AC: 40 AN: 23902 Hom.: 1 Cov.: 0 AF XY: 0.00162 AC XY: 20 AN XY: 12310

Gnomad4 AFR exome AF: 0.0300

Gnomad4 AMR exome AF: 0.00408

Gnomad4 ASJ exome AF: 0.00365

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000512

Gnomad4 OTH exome AF: 0.00371

GnomAD4 genome AF: 0.0350 AC: 5331 AN: 152180 Hom.: 296 Cov.: 32 AF XY: 0.0338 AC XY: 2516 AN XY: 74422

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.00433

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.00145

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00140

Gnomad4 OTH AF: 0.0284

Asia WGS AF: 0.00751 AC: 26 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 28, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs538199922; hg19: chr22-51021621;