rs9513675

Variant names:

• chr13-99840906-G-A
• rs9513675
• NM_206808.5:c.250-17955G>A

Variant summary

Our verdict is Benign. The variant received -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
• 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]

ENSG00000286757 (HGNC:):

CLYBL-AS3 (HGNC:56191): (CLYBL antisense RNA 3)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CLYBL	NM_206808.5	c.250-17955G>A		intron_variant	Intron 2 of 8	ENST00000339105.9	NP_996531.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLYBL	ENST00000339105.9	c.250-17955G>A		intron_variant	Intron 2 of 8	1	NM_206808.5	ENSP00000342991.4

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

African (AFR) AF: 0.728 AC: 30082 AN: 41340

American (AMR) AF: 0.583 AC: 8886 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.664 AC: 2304 AN: 3468

East Asian (EAS) AF: 0.722 AC: 3731 AN: 5166

South Asian (SAS) AF: 0.527 AC: 2522 AN: 4782

European-Finnish (FIN) AF: 0.566 AC: 5938 AN: 10500

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37867 AN: 67928

Other (OTH) AF: 0.636 AC: 1338 AN: 2104

Alfa AF: 0.586 Hom.: 74501

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
PhyloP100		-0.26
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: rs9513675; hg19: chr13-100493160;