rs3765459

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_001250.6(CD40):c.676-114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,156,138 control chromosomes in the GnomAD database, including 31,272 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.18 ( 3061 hom., cov: 31)

Exomes 𝑓: 0.23 ( 28211 hom. )

Consequence

CD40
NM_001250.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.97

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=-0.96).

BP6

Variant 20-46128768-G-A is Benign according to our data. Variant chr20-46128768-G-A is described in ClinVar as [Benign]. Clinvar id is 1261840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD40	NM_001250.6 link	c.676-114G>A		intron_variant	Intron 8 of 8	ENST00000372285.8	NP_001241.1	P25942-1A0A0S2Z3C7Q6P2H9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD40	ENST00000372285.8 link	c.676-114G>A		intron_variant	Intron 8 of 8	1	NM_001250.6	ENSP00000361359.3		P25942-1

Frequencies

GnomAD3 genomes

AF:

0.184

AC:

27985

AN:

151880

Hom.:

3056

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0627

Gnomad AMI

AF:

0.355

Gnomad AMR

AF:

0.157

Gnomad ASJ

AF:

0.228

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.237

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.179

GnomAD3 exomes

AF:

0.220

AC:

35321

AN:

160452

Hom.:

4208

AF XY:

0.228

AC XY:

19707

AN XY:

86452

show subpopulations

Gnomad AFR exome

AF:

0.0581

Gnomad AMR exome

AF:

0.122

Gnomad ASJ exome

AF:

0.229

Gnomad EAS exome

AF:

0.308

Gnomad SAS exome

AF:

0.270

Gnomad FIN exome

AF:

0.251

Gnomad NFE exome

AF:

0.243

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.231

AC:

231901

AN:

1004140

Hom.:

28211

Cov.:

AF XY:

0.233

AC XY:

119087

AN XY:

510964

show subpopulations

Gnomad4 AFR exome

AF:

0.0599

Gnomad4 AMR exome

AF:

0.125

Gnomad4 ASJ exome

AF:

0.230

Gnomad4 EAS exome

AF:

0.286

Gnomad4 SAS exome

AF:

0.268

Gnomad4 FIN exome

AF:

0.249

Gnomad4 NFE exome

AF:

0.236

Gnomad4 OTH exome

AF:

0.220

GnomAD4 genome

AF:

0.184

AC:

27995

AN:

151998

Hom.:

3061

Cov.:

AF XY:

0.186

AC XY:

13800

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0629

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.228

Gnomad4 EAS

AF:

0.293

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.246

Gnomad4 NFE

AF:

0.236

Gnomad4 OTH

AF:

0.179

Alfa

AF:

0.207

Hom.:

680

Bravo

AF:

0.173

Asia WGS

AF:

0.228

AC:

794

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

Aug 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.96

CADD

Benign

0.077

DANN

Benign

0.75

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