NM_001393360.1:c.*25-5271G>C

Variant names:

• chr13-99902784-G-C
• rs7992643
• NM_001393360.1:c.*25-5271G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001393360.1(CLYBL):​c.*25-5271G>C variant causes a intron 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 NM_001393360.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.909
• Publications: 17 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 -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 rank	MANE	Protein	UniProt
CLYBL	NM_001393360.1	c.*25-5271G>C		intron_variant	Intron 7 of 7		NP_001380289.1
CLYBL	NM_001393361.1	c.*25-2486G>C		intron_variant	Intron 7 of 7		NP_001380290.1
CLYBL	NR_104592.2	n.1054-2486G>C		intron_variant	Intron 8 of 9
CLYBL-AS3	NR_120421.1	n.83+54299C>G		intron_variant	Intron 1 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ENSG00000286757	ENST00000656974.1	n.192-47340C>G		intron_variant	Intron 1 of 2
ENSG00000286757	ENST00000659729.1	n.100-47340C>G		intron_variant	Intron 1 of 1
ENSG00000286757	ENST00000661077.2	n.106-47340C>G		intron_variant	Intron 1 of 2

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

African (AFR) AF: 0.640 AC: 26552 AN: 41504

American (AMR) AF: 0.435 AC: 6635 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.426 AC: 1476 AN: 3468

East Asian (EAS) AF: 0.528 AC: 2731 AN: 5172

South Asian (SAS) AF: 0.614 AC: 2959 AN: 4822

European-Finnish (FIN) AF: 0.407 AC: 4307 AN: 10576

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.363 AC: 24682 AN: 67978

Other (OTH) AF: 0.413 AC: 872 AN: 2110

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
PhyloP100		0.91

Splicing

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

Other links and lift over

dbSNP: rs7992643; hg19: chr13-100555038;