chr13-99828410-G-A

Variant names:

• chr13-99828410-G-A
• rs1555589
• NM_206808.5:c.250-30451G>A

Variant summary

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

The NM_206808.5(CLYBL):​c.250-30451G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.761 in 152,188 control chromosomes in the GnomAD database, including 45,345 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 0.76 (45345 hom., cov: 33)
• Consequence: CLYBL NM_206808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713
• Publications: 5 publications found

Genes affected

CLYBL (HGNC:18355): (citramalyl-CoA lyase) Enables (S)-citramalyl-CoA lyase activity; magnesium ion binding activity; and malate synthase activity. Involved in protein homotrimerization and regulation of cobalamin metabolic process. Predicted to be located in mitochondrion. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLYBL-AS3 (HGNC:56191): (CLYBL antisense RNA 3)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206808.5. 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
	CLYBL	NM_206808.5	MANE Select	c.250-30451G>A		intron	N/A	NP_996531.1
	CLYBL	NM_001393356.1		c.250-30451G>A		intron	N/A	NP_001380285.1
	CLYBL	NM_001393357.1		c.250-30451G>A		intron	N/A	NP_001380286.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLYBL	ENST00000339105.9	TSL:1 MANE Select	c.250-30451G>A		intron	N/A	ENSP00000342991.4
	CLYBL	ENST00000376355.7	TSL:2	c.250-30451G>A		intron	N/A	ENSP00000365533.4
	CLYBL	ENST00000376354.5	TSL:5	c.250-30451G>A		intron	N/A	ENSP00000365532.1

Frequencies

GnomAD3 genomes AF: 0.761 AC: 115768 AN: 152070 Hom.: 45298 Cov.: 33

Gnomad AFR AF: 0.934

Gnomad AMI AF: 0.818

Gnomad AMR AF: 0.741

Gnomad ASJ AF: 0.791

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.745

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.660

Gnomad OTH AF: 0.773

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.761 AC: 115872 AN: 152188 Hom.: 45345 Cov.: 33 AF XY: 0.763 AC XY: 56730 AN XY: 74396

African (AFR) AF: 0.935 AC: 38831 AN: 41550

American (AMR) AF: 0.740 AC: 11326 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 2747 AN: 3472

East Asian (EAS) AF: 0.933 AC: 4831 AN: 5178

South Asian (SAS) AF: 0.746 AC: 3595 AN: 4820

European-Finnish (FIN) AF: 0.665 AC: 7031 AN: 10576

Middle Eastern (MID) AF: 0.808 AC: 236 AN: 292

European-Non Finnish (NFE) AF: 0.660 AC: 44902 AN: 67982

Other (OTH) AF: 0.771 AC: 1627 AN: 2110

Alfa AF: 0.700 Hom.: 63627

Bravo AF: 0.775

Asia WGS AF: 0.836 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	8.7
DANN	Benign	0.69
PhyloP100		0.71
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs1555589; hg19: chr13-100480664;