rs13169284

Positions:

• chr5-10289925-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_138809.4(CMBL):​c.215+623C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 152,072 control chromosomes in the GnomAD database, including 19,124 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 0.44 (19124 hom., cov: 32)
• Consequence: CMBL NM_138809.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.384

Genes affected

CMBL (HGNC:25090): (carboxymethylenebutenolidase homolog) CMBL (EC 3.1.1.45) is a cysteine hydrolase of the dienelactone hydrolase family that is highly expressed in liver cytosol. CMBL preferentially cleaves cyclic esters, and it activates medoxomil-ester prodrugs in which the medoxomil moiety is linked to an oxygen atom (Ishizuka et al., 2010 [PubMed 20177059]).[supplied by OMIM, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CMBL	NM_138809.4	c.215+623C>T		intron_variant		ENST00000296658.4	NP_620164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CMBL	ENST00000296658.4	c.215+623C>T		intron_variant		1	NM_138809.4	ENSP00000296658	P1
CMBL	ENST00000506821.1	n.469+623C>T		intron_variant, non_coding_transcript_variant		2
CMBL	ENST00000510532.5	n.283+623C>T		intron_variant, non_coding_transcript_variant		3
CMBL	ENST00000511963.5	n.323+623C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67191 AN: 151954 Hom.: 19129 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.728

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.639

Gnomad EAS AF: 0.0617

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.544

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.461

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

GnomAD4 genome AF: 0.442 AC: 67175 AN: 152072 Hom.: 19124 Cov.: 32 AF XY: 0.438 AC XY: 32517 AN XY: 74322

Gnomad4 AFR AF: 0.121

Gnomad4 AMR AF: 0.396

Gnomad4 ASJ AF: 0.639

Gnomad4 EAS AF: 0.0618

Gnomad4 SAS AF: 0.337

Gnomad4 FIN AF: 0.624

Gnomad4 NFE AF: 0.642

Gnomad4 OTH AF: 0.458

Alfa AF: 0.568 Hom.: 17562

Bravo AF: 0.410

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.2
DANN	Benign	0.52

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: rs13169284; hg19: chr5-10290037;