NM_206808.5:c.63-51018A>C

Variant names:

• chr13-99721806-A-C
• rs1125436
• NM_206808.5:c.63-51018A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLYBL	NM_206808.5	c.63-51018A>C		intron_variant	Intron 1 of 8	ENST00000339105.9	NP_996531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLYBL	ENST00000339105.9	c.63-51018A>C		intron_variant	Intron 1 of 8	1	NM_206808.5	ENSP00000342991.4

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

African (AFR) AF: 0.195 AC: 8070 AN: 41418

American (AMR) AF: 0.198 AC: 3021 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 504 AN: 3470

East Asian (EAS) AF: 0.484 AC: 2489 AN: 5144

South Asian (SAS) AF: 0.339 AC: 1632 AN: 4812

European-Finnish (FIN) AF: 0.249 AC: 2623 AN: 10554

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11300 AN: 67956

Other (OTH) AF: 0.176 AC: 371 AN: 2108

Alfa AF: 0.174 Hom.: 4805

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
PhyloP100		-1.1
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: rs1125436; hg19: chr13-100374060;