rs5770917

Variant names:

• chr22-50578924-T-C
• rs5770917
• ENST00000453634.5:n.*145+112A>G

Your query was ambiguous. Multiple possible variants found:

• chr22-50578924-T-C
• chr22-50578924-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000453634.5(CHKB-CPT1B):​n.*145+112A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0692 in 559,868 control chromosomes in the GnomAD database, including 2,222 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.064 (495 hom., cov: 33)
  • Exomes 𝑓: 0.071 (1727 hom.)
• Consequence: CHKB-CPT1B ENST00000453634.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.60
• Publications: 42 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• megaconial type congenital muscular dystrophy

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 22-50578924-T-C is Benign according to our data. Variant chr22-50578924-T-C is described in ClinVar as Benign. ClinVar VariationId is 1231742.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHKB-CPT1B	NR_027928.2	n.1551+112A>G		intron_variant	Intron 11 of 29
CHKB	NM_005198.5	c.*257A>G		downstream_gene_variant		ENST00000406938.3	NP_005189.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHKB-CPT1B	ENST00000453634.5	n.*145+112A>G		intron_variant	Intron 3 of 22	5		ENSP00000457031.1
CHKB	ENST00000406938.3	c.*257A>G		downstream_gene_variant		1	NM_005198.5	ENSP00000384400.3

Frequencies

GnomAD3 genomes AF: 0.0639 AC: 9716 AN: 152158 Hom.: 494 Cov.: 33

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0424

Gnomad EAS AF: 0.255

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0476

Gnomad OTH AF: 0.0549

GnomAD4 exome AF: 0.0712 AC: 29005 AN: 407592 Hom.: 1727 Cov.: 0 AF XY: 0.0734 AC XY: 15890 AN XY: 216366

African (AFR) AF: 0.0502 AC: 577 AN: 11492

American (AMR) AF: 0.151 AC: 2694 AN: 17858

Ashkenazi Jewish (ASJ) AF: 0.0446 AC: 553 AN: 12402

East Asian (EAS) AF: 0.227 AC: 6159 AN: 27122

South Asian (SAS) AF: 0.110 AC: 5010 AN: 45516

European-Finnish (FIN) AF: 0.0520 AC: 1334 AN: 25652

Middle Eastern (MID) AF: 0.0448 AC: 79 AN: 1762

European-Non Finnish (NFE) AF: 0.0457 AC: 11082 AN: 242570

Other (OTH) AF: 0.0653 AC: 1517 AN: 23218

GnomAD4 genome AF: 0.0639 AC: 9732 AN: 152276 Hom.: 495 Cov.: 33 AF XY: 0.0663 AC XY: 4934 AN XY: 74460

African (AFR) AF: 0.0496 AC: 2061 AN: 41558

American (AMR) AF: 0.108 AC: 1660 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0424 AC: 147 AN: 3470

East Asian (EAS) AF: 0.255 AC: 1319 AN: 5170

South Asian (SAS) AF: 0.127 AC: 614 AN: 4830

European-Finnish (FIN) AF: 0.0520 AC: 552 AN: 10622

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0476 AC: 3239 AN: 68006

Other (OTH) AF: 0.0572 AC: 121 AN: 2116

Alfa AF: 0.0559 Hom.: 850

Bravo AF: 0.0689

Asia WGS AF: 0.178 AC: 619 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Jun 29, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.3
DANN	Benign	0.80
PhyloP100		-1.6
PromoterAI		0.0016	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs5770917; hg19: chr22-51017353;