rs2761171

Positions:

• chr13-99828643-G-A
• chr13-99828643-G-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_206808.5(CLYBL):​c.250-30218G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 151,964 control chromosomes in the GnomAD database, including 29,869 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 0.62 (29869 hom., cov: 32)
• Consequence: CLYBL NM_206808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLYBL	NM_206808.5	c.250-30218G>A		intron_variant		ENST00000339105.9
CLYBL-AS3	NR_120421.1	n.84-53295C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLYBL	ENST00000339105.9	c.250-30218G>A		intron_variant		1	NM_206808.5	P1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94628 AN: 151846 Hom.: 29862 Cov.: 32

Gnomad AFR AF: 0.696

Gnomad AMI AF: 0.741

Gnomad AMR AF: 0.603

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.745

Gnomad SAS AF: 0.596

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.715

Gnomad NFE AF: 0.582

Gnomad OTH AF: 0.643

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

GnomAD4 genome AF: 0.623 AC: 94676 AN: 151964 Hom.: 29869 Cov.: 32 AF XY: 0.622 AC XY: 46219 AN XY: 74282

Gnomad4 AFR AF: 0.696

Gnomad4 AMR AF: 0.602

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.745

Gnomad4 SAS AF: 0.595

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.582

Gnomad4 OTH AF: 0.642

Alfa AF: 0.600 Hom.: 53378

Bravo AF: 0.630

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.73

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: rs2761171; hg19: chr13-100480897; COSMIC: COSV59227051;