rs9513675

chr13-99840906-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.250-17955G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.616 in 151,728 control chromosomes in the GnomAD database, including 29,349 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 (29349 hom., cov: 30)
• Consequence: CLYBL NM_206808.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.255

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.721 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLYBL	NM_206808.5	c.250-17955G>A		intron_variant		ENST00000339105.9
CLYBL-AS3	NR_120421.1	n.84-65558C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLYBL	ENST00000339105.9	c.250-17955G>A		intron_variant		1	NM_206808.5	P1
	ENST00000670400.1	n.70+275C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.616 AC: 93416 AN: 151612 Hom.: 29330 Cov.: 30

Gnomad AFR AF: 0.728

Gnomad AMI AF: 0.664

Gnomad AMR AF: 0.584

Gnomad ASJ AF: 0.664

Gnomad EAS AF: 0.723

Gnomad SAS AF: 0.528

Gnomad FIN AF: 0.566

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.635

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

GnomAD4 genome AF: 0.616 AC: 93483 AN: 151728 Hom.: 29349 Cov.: 30 AF XY: 0.615 AC XY: 45611 AN XY: 74136

Gnomad4 AFR AF: 0.728

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.664

Gnomad4 EAS AF: 0.722

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.566

Gnomad4 NFE AF: 0.557

Gnomad4 OTH AF: 0.636

Alfa AF: 0.581 Hom.: 26287

Bravo AF: 0.624

Asia WGS AF: 0.640 AC: 2226 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	2.1
Dann	Benign	0.48

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: rs9513675; hg19: chr13-100493160;