NM_001250.6:c.51+71C>A

Variant names:

• chr20-46118465-C-A
• rs11569302
• NM_001250.6:c.51+71C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001250.6(CD40):​c.51+71C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CD40 NM_001250.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.751
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 3

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001250.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD40	NM_001250.6	MANE Select	c.51+71C>A		intron	N/A	NP_001241.1	P25942-1
	CD40	NM_001322421.2		c.51+71C>A		intron	N/A	NP_001309350.1
	CD40	NM_001302753.2		c.51+71C>A		intron	N/A	NP_001289682.1	A0A8Q3SI60

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD40	ENST00000372285.8	TSL:1 MANE Select	c.51+71C>A		intron	N/A	ENSP00000361359.3	P25942-1
	CD40	ENST00000372276.7	TSL:1	c.51+71C>A		intron	N/A	ENSP00000361350.3	P25942-2
	CD40	ENST00000466205.5	TSL:1	n.45+71C>A		intron	N/A	ENSP00000434825.1	H0YE23

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 778498 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 405108

African (AFR) AF: 0.00 AC: 0 AN: 19528

American (AMR) AF: 0.00 AC: 0 AN: 37624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15512

East Asian (EAS) AF: 0.00 AC: 0 AN: 16174

South Asian (SAS) AF: 0.00 AC: 0 AN: 73586

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36734

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 544338

Other (OTH) AF: 0.00 AC: 0 AN: 31306

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.68
PhyloP100		-0.75
PromoterAI		-0.020	Neutral

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

Other links and lift over

dbSNP: rs11569302; hg19: chr20-44747104;