rs6020846

Variant names:

• chr20-37777265-A-G
• rs6020846
• NM_030877.5:c.751-80A>G

Variant summary

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

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]

CTNNBL1 Gene-Disease associations (from GenCC):

• common variable immunodeficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen
• immunodeficiency 99 with hypogammaglobulinemia and autoimmune cytopenias

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.751-80A>G		intron_variant	Intron 7 of 15	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.670-80A>G		intron_variant	Intron 8 of 16		NP_001268424.1
CTNNBL1	XM_024451947.2	c.670-80A>G		intron_variant	Intron 8 of 16		XP_024307715.1
CTNNBL1	XM_011528917.3	c.421-80A>G		intron_variant	Intron 5 of 13		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.751-80A>G		intron_variant	Intron 7 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.670-80A>G		intron_variant	Intron 8 of 16	2		ENSP00000487198.1

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

African (AFR) AF: 0.265 AC: 5995 AN: 22650

American (AMR) AF: 0.0529 AC: 2293 AN: 43332

Ashkenazi Jewish (ASJ) AF: 0.0422 AC: 937 AN: 22210

East Asian (EAS) AF: 0.0121 AC: 449 AN: 37100

South Asian (SAS) AF: 0.0311 AC: 2305 AN: 74072

European-Finnish (FIN) AF: 0.0675 AC: 3496 AN: 51770

Middle Eastern (MID) AF: 0.0711 AC: 333 AN: 4682

European-Non Finnish (NFE) AF: 0.0604 AC: 37328 AN: 617992

Other (OTH) AF: 0.0751 AC: 3171 AN: 42212

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

African (AFR) AF: 0.270 AC: 11192 AN: 41494

American (AMR) AF: 0.0780 AC: 1193 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3468

East Asian (EAS) AF: 0.0104 AC: 54 AN: 5184

South Asian (SAS) AF: 0.0318 AC: 153 AN: 4814

European-Finnish (FIN) AF: 0.0738 AC: 782 AN: 10594

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0647 AC: 4396 AN: 67994

Other (OTH) AF: 0.121 AC: 256 AN: 2116

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
PhyloP100		-0.20
PromoterAI		0.040	Neutral
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: rs6020846; hg19: chr20-36405667;