chr20-37746669-T-C

Variant names:

• chr20-37746669-T-C
• rs2297154
• NM_030877.5:c.466+62T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030877.5(CTNNBL1):​c.466+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.938 in 1,582,316 control chromosomes in the GnomAD database, including 697,335 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.95 (69421 hom., cov: 32)
  • Exomes 𝑓: 0.94 (627914 hom.)
• Consequence: CTNNBL1 NM_030877.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00200
• Publications: 8 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 20-37746669-T-C is Benign according to our data. Variant chr20-37746669-T-C is described in ClinVar as Benign. ClinVar VariationId is 2687972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030877.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	NM_030877.5	MANE Select	c.466+62T>C		intron	N/A	NP_110517.2
	CTNNBL1	NM_001281495.2		c.385+62T>C		intron	N/A	NP_001268424.1	Q8WYA6-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CTNNBL1	ENST00000361383.11	TSL:1 MANE Select	c.466+62T>C		intron	N/A	ENSP00000355050.6	Q8WYA6-1
	CTNNBL1	ENST00000628103.2	TSL:2	c.385+62T>C		intron	N/A	ENSP00000487198.1	Q8WYA6-4
	CTNNBL1	ENST00000373473.5	TSL:1	c.3+22T>C		intron	N/A	ENSP00000362572.1	Q8WYA6-2

Frequencies

GnomAD3 genomes AF: 0.954 AC: 145228 AN: 152218 Hom.: 69361 Cov.: 32

Gnomad AFR AF: 0.988

Gnomad AMI AF: 0.889

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.873

Gnomad EAS AF: 0.975

Gnomad SAS AF: 0.909

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.938

Gnomad OTH AF: 0.934

GnomAD2 exomes AF: 0.944 AC: 235875 AN: 249972 AF XY: 0.938

Gnomad AFR exome AF: 0.989

Gnomad AMR exome AF: 0.966

Gnomad ASJ exome AF: 0.880

Gnomad EAS exome AF: 0.979

Gnomad FIN exome AF: 0.979

Gnomad NFE exome AF: 0.937

Gnomad OTH exome AF: 0.929

GnomAD4 exome AF: 0.937 AC: 1339389 AN: 1429980 Hom.: 627914 Cov.: 23 AF XY: 0.934 AC XY: 666683 AN XY: 713550

African (AFR) AF: 0.988 AC: 32438 AN: 32818

American (AMR) AF: 0.965 AC: 43086 AN: 44634

Ashkenazi Jewish (ASJ) AF: 0.880 AC: 22828 AN: 25944

East Asian (EAS) AF: 0.964 AC: 38100 AN: 39522

South Asian (SAS) AF: 0.896 AC: 76543 AN: 85404

European-Finnish (FIN) AF: 0.979 AC: 52245 AN: 53368

Middle Eastern (MID) AF: 0.813 AC: 4642 AN: 5708

European-Non Finnish (NFE) AF: 0.936 AC: 1014203 AN: 1083248

Other (OTH) AF: 0.932 AC: 55304 AN: 59334

GnomAD4 genome AF: 0.954 AC: 145347 AN: 152336 Hom.: 69421 Cov.: 32 AF XY: 0.955 AC XY: 71126 AN XY: 74484

African (AFR) AF: 0.988 AC: 41064 AN: 41576

American (AMR) AF: 0.952 AC: 14556 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.873 AC: 3031 AN: 3470

East Asian (EAS) AF: 0.975 AC: 5053 AN: 5184

South Asian (SAS) AF: 0.909 AC: 4389 AN: 4830

European-Finnish (FIN) AF: 0.982 AC: 10429 AN: 10622

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.938 AC: 63802 AN: 68044

Other (OTH) AF: 0.935 AC: 1977 AN: 2114

Alfa AF: 0.938 Hom.: 20880

Bravo AF: 0.954

Asia WGS AF: 0.948 AC: 3294 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.2
DANN	Benign	0.62
PhyloP100		0.0020
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: rs2297154; hg19: chr20-36375071;