rs6125962

Variant names:

• chr20-37712660-T-C
• rs6125962
• NM_030877.5:c.30+18508T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030877.5(CTNNBL1):​c.30+18508T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.155 in 152,228 control chromosomes in the GnomAD database, including 3,399 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 0.15 (3399 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.269
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.30+18508T>C		intron_variant	Intron 1 of 15	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.-152-14642T>C		intron_variant	Intron 1 of 16		NP_001268424.1
CTNNBL1	XM_024451947.2	c.-52+17627T>C		intron_variant	Intron 2 of 16		XP_024307715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.30+18508T>C		intron_variant	Intron 1 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.-152-14642T>C		intron_variant	Intron 1 of 16	2		ENSP00000487198.1
CTNNBL1	ENST00000447935.3	c.-52+17627T>C		intron_variant	Intron 2 of 6	5		ENSP00000394464.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23523 AN: 152110 Hom.: 3390 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.0969

Gnomad ASJ AF: 0.0242

Gnomad EAS AF: 0.0292

Gnomad SAS AF: 0.0337

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0646

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.155 AC: 23569 AN: 152228 Hom.: 3399 Cov.: 32 AF XY: 0.151 AC XY: 11237 AN XY: 74448

African (AFR) AF: 0.383 AC: 15895 AN: 41472

American (AMR) AF: 0.0970 AC: 1484 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0242 AC: 84 AN: 3472

East Asian (EAS) AF: 0.0293 AC: 152 AN: 5190

South Asian (SAS) AF: 0.0335 AC: 162 AN: 4834

European-Finnish (FIN) AF: 0.0773 AC: 821 AN: 10616

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0646 AC: 4396 AN: 68028

Other (OTH) AF: 0.142 AC: 301 AN: 2114

Alfa AF: 0.107 Hom.: 360

Bravo AF: 0.166

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.0
DANN	Benign	0.55
PhyloP100		-0.27
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: rs6125962; hg19: chr20-36341062;