rs16986921

Variant names:

• chr20-37754119-C-T
• rs16986921
• NM_030877.5:c.467-3440C>T

Variant summary

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

The NM_030877.5(CTNNBL1):​c.467-3440C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,062 control chromosomes in the GnomAD database, including 1,666 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 0.11 (1666 hom., cov: 32)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.357
• Publications: 10 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)

LOC124904895 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.467-3440C>T		intron_variant	Intron 4 of 15	ENST00000361383.11	NP_110517.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.467-3440C>T		intron_variant	Intron 4 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.386-3440C>T		intron_variant	Intron 5 of 16	2		ENSP00000487198.1
CTNNBL1	ENST00000447935.3	c.386-3440C>T		intron_variant	Intron 5 of 6	5		ENSP00000394464.1

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17122 AN: 151944 Hom.: 1659 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.0182

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.0675

Gnomad MID AF: 0.0860

Gnomad NFE AF: 0.0554

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.113 AC: 17160 AN: 152062 Hom.: 1666 Cov.: 32 AF XY: 0.110 AC XY: 8200 AN XY: 74374

African (AFR) AF: 0.266 AC: 11015 AN: 41422

American (AMR) AF: 0.0659 AC: 1008 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0182 AC: 63 AN: 3470

East Asian (EAS) AF: 0.0100 AC: 52 AN: 5188

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4828

European-Finnish (FIN) AF: 0.0675 AC: 713 AN: 10566

Middle Eastern (MID) AF: 0.0822 AC: 24 AN: 292

European-Non Finnish (NFE) AF: 0.0554 AC: 3766 AN: 67994

Other (OTH) AF: 0.110 AC: 231 AN: 2102

Alfa AF: 0.109 Hom.: 329

Bravo AF: 0.120

Asia WGS AF: 0.0420 AC: 144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.9
DANN	Benign	0.18
PhyloP100		0.36
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: rs16986921; hg19: chr20-36382521;