13-99902784-G-C

Position:

• chr13-99902784-G-C

Variant summary

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

The NR_120421.1(CLYBL-AS3):​n.83+54299C>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.464 in 152,104 control chromosomes in the GnomAD database, including 17,732 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 0.46 (17732 hom., cov: 33)
• Consequence: CLYBL-AS3 NR_120421.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909

Genes affected

(HGNC:):

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.633 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLYBL-AS3	NR_120421.1	n.83+54299C>G		intron_variant, non_coding_transcript_variant
CLYBL	NM_001393360.1	c.*25-5271G>C		intron_variant			NP_001380289.1
CLYBL	NM_001393361.1	c.*25-2486G>C		intron_variant			NP_001380290.1
CLYBL	NR_104592.2	n.1054-2486G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
	ENST00000670575.1	n.86-47340C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70542 AN: 151986 Hom.: 17699 Cov.: 33

Gnomad AFR AF: 0.640

Gnomad AMI AF: 0.305

Gnomad AMR AF: 0.434

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.407

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.363

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.464 AC: 70631 AN: 152104 Hom.: 17732 Cov.: 33 AF XY: 0.471 AC XY: 35024 AN XY: 74350

Gnomad4 AFR AF: 0.640

Gnomad4 AMR AF: 0.435

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.528

Gnomad4 SAS AF: 0.614

Gnomad4 FIN AF: 0.407

Gnomad4 NFE AF: 0.363

Gnomad4 OTH AF: 0.413

Alfa AF: 0.364 Hom.: 5334

Bravo AF: 0.472

Asia WGS AF: 0.559 AC: 1944 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.79

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7992643; hg19: chr13-100555038;