rs1555589

chr13-99828410-G-A

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLYBL	NM_206808.5	c.250-30451G>A		intron_variant		ENST00000339105.9
CLYBL-AS3	NR_120421.1	n.84-53062C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLYBL	ENST00000339105.9	c.250-30451G>A		intron_variant		1	NM_206808.5	P1

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

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.740

Gnomad4 ASJ AF: 0.791

Gnomad4 EAS AF: 0.933

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.665

Gnomad4 NFE AF: 0.660

Gnomad4 OTH AF: 0.771

Alfa AF: 0.694 Hom.: 49202

Bravo AF: 0.775

Asia WGS AF: 0.836 AC: 2907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
Cadd	Benign	8.7
Dann	Benign	0.69

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555589; hg19: chr13-100480664;