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

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

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;