Variant 20-46118447-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001250.6(CD40):c.51+53G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,443,336 control chromosomes in the GnomAD database, including 46,725 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 2950 hom., cov: 32)

Exomes 𝑓: 0.26 ( 43775 hom. )

Consequence

CD40
NM_001250.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.382

Variant links:

Genes affected

CD40 (HGNC:11919): (CD40 molecule) This gene is a member of the TNF-receptor superfamily. The encoded protein is a receptor on antigen-presenting cells of the immune system and is essential for mediating a broad variety of immune and inflammatory responses including T cell-dependent immunoglobulin class switching, memory B cell development, and germinal center formation. AT-hook transcription factor AKNA is reported to coordinately regulate the expression of this receptor and its ligand, which may be important for homotypic cell interactions. Adaptor protein TNFR2 interacts with this receptor and serves as a mediator of the signal transduction. The interaction of this receptor and its ligand is found to be necessary for amyloid-beta-induced microglial activation, and thus is thought to be an early event in Alzheimer disease pathogenesis. Mutations affecting this gene are the cause of autosomal recessive hyper-IgM immunodeficiency type 3 (HIGM3). Multiple alternatively spliced transcript variants of this gene encoding distinct isoforms have been reported. [provided by RefSeq, Nov 2014]

CD40 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 20-46118447-G-A is Benign according to our data. Variant chr20-46118447-G-A is described in ClinVar as [Benign]. Clinvar id is 1245520.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CD40	NM_001250.6 linkuse as main transcript	c.51+53G>A		intron_variant		ENST00000372285.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CD40	ENST00000372285.8 linkuse as main transcript	c.51+53G>A		intron_variant		1	NM_001250.6	P1	P25942-1

Frequencies

GnomAD3 genomes

AF:

0.180

AC:

26856

AN:

149476

Hom.:

2949

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0653

Gnomad AMI

AF:

0.237

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.186

Gnomad EAS

AF:

0.0337

Gnomad SAS

AF:

0.183

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.178

Gnomad NFE

AF:

0.258

Gnomad OTH

AF:

0.187

GnomAD4 exome

AF:

0.262

AC:

338338

AN:

1293722

Hom.:

43775

AF XY:

0.261

AC XY:

168537

AN XY:

645632

show subpopulations

Gnomad4 AFR exome

AF:

0.0690

Gnomad4 AMR exome

AF:

0.109

Gnomad4 ASJ exome

AF:

0.221

Gnomad4 EAS exome

AF:

0.0610

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.308

Gnomad4 NFE exome

AF:

0.284

Gnomad4 OTH exome

AF:

0.248

GnomAD4 genome

AF:

0.179

AC:

26853

AN:

149614

Hom.:

2950

Cov.:

AF XY:

0.177

AC XY:

12914

AN XY:

73116

show subpopulations

Gnomad4 AFR

AF:

0.0652

Gnomad4 AMR

AF:

0.126

Gnomad4 ASJ

AF:

0.186

Gnomad4 EAS

AF:

0.0336

Gnomad4 SAS

AF:

0.184

Gnomad4 FIN

AF:

0.259

Gnomad4 NFE

AF:

0.258

Gnomad4 OTH

AF:

0.183

Alfa

AF:

0.228

Hom.:

4105

Bravo

AF:

0.163

Asia WGS

AF:

0.100

AC:

349

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 08, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 28% of patients studied by a panel of primary immunodeficiencies. Number of patients: 27. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

DANN

Benign

0.72

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over