chr20-37746669-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CTNNBL1	NM_030877.5	c.466+62T>C		intron_variant	Intron 4 of 15	ENST00000361383.11	NP_110517.2
CTNNBL1	NM_001281495.2	c.385+62T>C		intron_variant	Intron 5 of 16		NP_001268424.1
CTNNBL1	XM_024451947.2	c.385+62T>C		intron_variant	Intron 5 of 16		XP_024307715.1
CTNNBL1	XM_011528917.3	c.136+62T>C		intron_variant	Intron 2 of 13		XP_011527219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CTNNBL1	ENST00000361383.11	c.466+62T>C		intron_variant	Intron 4 of 15	1	NM_030877.5	ENSP00000355050.6
CTNNBL1	ENST00000628103.2	c.385+62T>C		intron_variant	Intron 5 of 16	2		ENSP00000487198.1
CTNNBL1	ENST00000447935.3	c.385+62T>C		intron_variant	Intron 5 of 6	5		ENSP00000394464.1

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

GnomAD3 exomes AF: 0.944 AC: 235875 AN: 249972 Hom.: 111483 AF XY: 0.938 AC XY: 126789 AN XY: 135188

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 SAS exome AF: 0.895

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

Gnomad4 AFR exome AF: 0.988

Gnomad4 AMR exome AF: 0.965

Gnomad4 ASJ exome AF: 0.880

Gnomad4 EAS exome AF: 0.964

Gnomad4 SAS exome AF: 0.896

Gnomad4 FIN exome AF: 0.979

Gnomad4 NFE exome AF: 0.936

Gnomad4 OTH exome AF: 0.932

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

Gnomad4 AFR AF: 0.988

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.873

Gnomad4 EAS AF: 0.975

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.938

Gnomad4 OTH AF: 0.935

Alfa AF: 0.938 Hom.: 20880

Bravo AF: 0.954

Asia WGS AF: 0.948 AC: 3294 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 100% of patients studied by a panel of primary immunodeficiencies. Number of patients: 95. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.2
DANN	Benign	0.62

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: rs2297154; hg19: chr20-36375071;