rs1125436

Positions:

• chr13-99721806-A-C
• chr13-99721806-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206808.5(CLYBL):​c.63-51018A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.199 in 151,948 control chromosomes in the GnomAD database, including 3,334 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 0.20 (3334 hom., cov: 31)
• Consequence: CLYBL NM_206808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLYBL	NM_206808.5	c.63-51018A>C		intron_variant		ENST00000339105.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLYBL	ENST00000339105.9	c.63-51018A>C		intron_variant		1	NM_206808.5	P1

Frequencies

GnomAD3 genomes AF: 0.199 AC: 30174 AN: 151830 Hom.: 3335 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.484

Gnomad SAS AF: 0.339

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.199 AC: 30182 AN: 151948 Hom.: 3334 Cov.: 31 AF XY: 0.207 AC XY: 15333 AN XY: 74246

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.176

Alfa AF: 0.168 Hom.: 3205

Bravo AF: 0.194

Asia WGS AF: 0.378 AC: 1311 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.58
DANN	Benign	0.59

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: rs1125436; hg19: chr13-100374060;