Variant chr20-46128574-A-G 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.675+216A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 711,102 control chromosomes in the GnomAD database, including 6,865 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1138 hom., cov: 30)

Exomes 𝑓: 0.14 ( 5727 hom. )

Consequence

CD40
NM_001250.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.24

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=-0.95).

BP6

Variant 20-46128574-A-G is Benign according to our data. Variant chr20-46128574-A-G is described in ClinVar as [Benign]. Clinvar id is 1236220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD40	NM_001250.6 linkuse as main transcript	c.675+216A>G		intron_variant		ENST00000372285.8	NP_001241.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD40	ENST00000372285.8 linkuse as main transcript	c.675+216A>G		intron_variant		1	NM_001250.6	ENSP00000361359	P1	P25942-1

Frequencies

GnomAD3 genomes

AF:

0.114

AC:

17303

AN:

151844

Hom.:

1137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0524

Gnomad AMI

AF:

0.0780

Gnomad AMR

AF:

0.0763

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.0313

Gnomad SAS

AF:

0.119

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.121

GnomAD3 exomes

AF:

0.118

AC:

15829

AN:

134174

Hom.:

1132

AF XY:

0.123

AC XY:

8854

AN XY:

72082

show subpopulations

Gnomad AFR exome

AF:

0.0408

Gnomad AMR exome

AF:

0.0600

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.0297

Gnomad SAS exome

AF:

0.130

Gnomad FIN exome

AF:

0.140

Gnomad NFE exome

AF:

0.157

Gnomad OTH exome

AF:

0.129

GnomAD4 exome

AF:

0.136

AC:

75804

AN:

559142

Hom.:

5727

Cov.:

AF XY:

0.136

AC XY:

41224

AN XY:

302100

show subpopulations

Gnomad4 AFR exome

AF:

0.0496

Gnomad4 AMR exome

AF:

0.0646

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0364

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.144

Gnomad4 NFE exome

AF:

0.156

Gnomad4 OTH exome

AF:

0.134

GnomAD4 genome

AF:

0.114

AC:

17307

AN:

151960

Hom.:

1138

Cov.:

AF XY:

0.110

AC XY:

8206

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.0524

Gnomad4 AMR

AF:

0.0762

Gnomad4 ASJ

AF:

0.162

Gnomad4 EAS

AF:

0.0312

Gnomad4 SAS

AF:

0.119

Gnomad4 FIN

AF:

0.140

Gnomad4 NFE

AF:

0.160

Gnomad4 OTH

AF:

0.119

Alfa

AF:

0.142

Hom.:

1583

Bravo

AF:

0.106

Asia WGS

AF:

0.0810

AC:

281

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 24, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.35

DANN

Benign

0.67

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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