rs6020846

Positions:

• chr20-37777265-A-G

Variant summary

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

The NM_030877.5(CTNNBL1):​c.751-80A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 1,068,174 control chromosomes in the GnomAD database, including 4,235 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 0.12 (1806 hom., cov: 32)
  • Exomes 𝑓: 0.061 (2429 hom.)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.200

Genes affected

CTNNBL1 (HGNC:15879): (catenin beta like 1) The protein encoded by this gene is a component of the pre-mRNA-processing factor 19-cell division cycle 5-like (PRP19-CDC5L) protein complex, which activates pre-mRNA splicing and is an integral part of the spliceosome. The encoded protein is also a nuclear localization sequence binding protein, and binds to activation-induced deaminase and is important for antibody diversification. This gene may also be associated with the development of obesity. Alternative splicing results in multiple transcript variants. A pseudogene of this gene has been defined on the X chromosome. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.266 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.751-80A>G		intron_variant		ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.670-80A>G		intron_variant			NP_001268424.1
CTNNBL1	XM_011528917.3	c.421-80A>G		intron_variant			XP_011527219.1
CTNNBL1	XM_024451947.2	c.670-80A>G		intron_variant			XP_024307715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.751-80A>G		intron_variant		1	NM_030877.5	ENSP00000355050	P1

Frequencies

GnomAD3 genomes AF: 0.121 AC: 18381 AN: 152036 Hom.: 1799 Cov.: 32

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.0318

Gnomad FIN AF: 0.0738

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.123

GnomAD4 exome AF: 0.0615 AC: 56307 AN: 916020 Hom.: 2429 Cov.: 12 AF XY: 0.0595 AC XY: 28442 AN XY: 477878

Gnomad4 AFR exome AF: 0.265

Gnomad4 AMR exome AF: 0.0529

Gnomad4 ASJ exome AF: 0.0422

Gnomad4 EAS exome AF: 0.0121

Gnomad4 SAS exome AF: 0.0311

Gnomad4 FIN exome AF: 0.0675

Gnomad4 NFE exome AF: 0.0604

Gnomad4 OTH exome AF: 0.0751

GnomAD4 genome AF: 0.121 AC: 18418 AN: 152154 Hom.: 1806 Cov.: 32 AF XY: 0.119 AC XY: 8819 AN XY: 74384

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.0780

Gnomad4 ASJ AF: 0.0349

Gnomad4 EAS AF: 0.0104

Gnomad4 SAS AF: 0.0318

Gnomad4 FIN AF: 0.0738

Gnomad4 NFE AF: 0.0647

Gnomad4 OTH AF: 0.121

Alfa AF: 0.0957 Hom.: 186

Bravo AF: 0.129

Asia WGS AF: 0.0420 AC: 146 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.6
DANN	Benign	0.28

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: rs6020846; hg19: chr20-36405667;