rs6074028

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001250.6(CD40):​c.498-421A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.039 ( 0 hom., cov: 18)
Failed GnomAD Quality Control

Consequence

CD40
NM_001250.6 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.725
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD40NM_001250.6 linkuse as main transcriptc.498-421A>C intron_variant ENST00000372285.8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD40ENST00000372285.8 linkuse as main transcriptc.498-421A>C intron_variant 1 NM_001250.6 P1P25942-1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
3051
AN:
78600
Hom.:
0
Cov.:
18
FAILED QC
Gnomad AFR
AF:
0.0497
Gnomad AMI
AF:
0.0374
Gnomad AMR
AF:
0.0295
Gnomad ASJ
AF:
0.0345
Gnomad EAS
AF:
0.0102
Gnomad SAS
AF:
0.0203
Gnomad FIN
AF:
0.0217
Gnomad MID
AF:
0.00521
Gnomad NFE
AF:
0.0420
Gnomad OTH
AF:
0.0403
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0388
AC:
3051
AN:
78664
Hom.:
0
Cov.:
18
AF XY:
0.0361
AC XY:
1374
AN XY:
38016
show subpopulations
Gnomad4 AFR
AF:
0.0495
Gnomad4 AMR
AF:
0.0295
Gnomad4 ASJ
AF:
0.0345
Gnomad4 EAS
AF:
0.0102
Gnomad4 SAS
AF:
0.0203
Gnomad4 FIN
AF:
0.0217
Gnomad4 NFE
AF:
0.0420
Gnomad4 OTH
AF:
0.0398

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.14
DANN
Benign
0.57

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.

Other links and lift over

dbSNP: rs6074028; hg19: chr20-44754858; API