rs2761171

Variant names:

• chr13-99828643-G-A
• rs2761171
• NM_206808.5:c.250-30218G>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 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]

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=-0.37).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.725 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206808.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLYBL	NM_206808.5	MANE Select	c.250-30218G>A		intron	N/A	NP_996531.1	Q8N0X4-1
	CLYBL	NM_001393356.1		c.250-30218G>A		intron	N/A	NP_001380285.1	Q8N0X4-1
	CLYBL	NM_001393357.1		c.250-30218G>A		intron	N/A	NP_001380286.1	Q8N0X4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLYBL	ENST00000339105.9	TSL:1 MANE Select	c.250-30218G>A		intron	N/A	ENSP00000342991.4	Q8N0X4-1
	CLYBL	ENST00000933047.1		c.250-30218G>A		intron	N/A	ENSP00000603106.1
	CLYBL	ENST00000898531.1		c.250-30218G>A		intron	N/A	ENSP00000568590.1

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

African (AFR) AF: 0.696 AC: 28833 AN: 41422

American (AMR) AF: 0.602 AC: 9201 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2443 AN: 3466

East Asian (EAS) AF: 0.745 AC: 3851 AN: 5172

South Asian (SAS) AF: 0.595 AC: 2865 AN: 4814

European-Finnish (FIN) AF: 0.542 AC: 5722 AN: 10552

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

European-Non Finnish (NFE) AF: 0.582 AC: 39521 AN: 67938

Other (OTH) AF: 0.642 AC: 1357 AN: 2114

Alfa AF: 0.600 Hom.: 73350

Bravo AF: 0.630

Asia WGS AF: 0.665 AC: 2310 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	17
DANN	Benign	0.73
PhyloP100		2.3
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: rs2761171; hg19: chr13-100480897; COSMIC: COSV59227051;