rs180979987

Variant names:

• chr22-50582333-G-A
• rs180979987
• NM_005198.5:c.249C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-50582333-G-A
• chr22-50582333-G-T

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The ENST00000406938.3(CHKB):​c.249C>T​(p.Phe83Phe) variant causes a synonymous change. The variant allele was found at a frequency of 0.00307 in 1,574,022 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0017 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (7 hom.)
• Consequence: CHKB ENST00000406938.3 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.59
• Publications: 0 publications found

Genes affected

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

Our verdict: Benign. The variant received -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 22-50582333-G-A is Benign according to our data. Variant chr22-50582333-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 342176.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00171 (260/152270) while in subpopulation NFE AF = 0.00338 (230/68000). AF 95% confidence interval is 0.00302. There are 1 homozygotes in GnomAd4. There are 104 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 7 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000406938.3. 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
	CHKB	NM_005198.5	MANE Select	c.249C>T	p.Phe83Phe	synonymous	Exon 2 of 11	NP_005189.2
	CHKB-CPT1B	NR_027928.2		n.467C>T		non_coding_transcript_exon	Exon 2 of 30

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHKB	ENST00000406938.3	TSL:1 MANE Select	c.249C>T	p.Phe83Phe	synonymous	Exon 2 of 11	ENSP00000384400.3
	CHKB	ENST00000481673.5	TSL:1	n.313C>T		non_coding_transcript_exon	Exon 2 of 10
	CHKB	ENST00000463053.1	TSL:3	n.331C>T		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes AF: 0.00171 AC: 260 AN: 152152 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00338

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00187 AC: 338 AN: 180366 AF XY: 0.00176

Gnomad AFR exome AF: 0.000189

Gnomad AMR exome AF: 0.0000365

Gnomad ASJ exome AF: 0.00126

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000528

Gnomad NFE exome AF: 0.00410

Gnomad OTH exome AF: 0.00146

GnomAD4 exome AF: 0.00321 AC: 4565 AN: 1421752 Hom.: 7 Cov.: 32 AF XY: 0.00310 AC XY: 2182 AN XY: 703948

African (AFR) AF: 0.000244 AC: 8 AN: 32746

American (AMR) AF: 0.000128 AC: 5 AN: 38940

Ashkenazi Jewish (ASJ) AF: 0.00122 AC: 31 AN: 25366

East Asian (EAS) AF: 0.00 AC: 0 AN: 37956

South Asian (SAS) AF: 0.0000123 AC: 1 AN: 81014

European-Finnish (FIN) AF: 0.000498 AC: 24 AN: 48204

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4302

European-Non Finnish (NFE) AF: 0.00402 AC: 4397 AN: 1094420

Other (OTH) AF: 0.00168 AC: 99 AN: 58804

GnomAD4 genome AF: 0.00171 AC: 260 AN: 152270 Hom.: 1 Cov.: 33 AF XY: 0.00140 AC XY: 104 AN XY: 74462

African (AFR) AF: 0.000505 AC: 21 AN: 41574

American (AMR) AF: 0.000196 AC: 3 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000865 AC: 3 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00338 AC: 230 AN: 68000

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00267 Hom.: 0

Bravo AF: 0.00178

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Megaconial type congenital muscular dystrophy (2)
-	-	2	not provided (2)
-	-	1	CHKB-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		4.6
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs180979987; hg19: chr22-51020762;