rs3092933

Positions:

• chrX-136655058-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000074.3(CD40LG):​c.346+628G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 110,850 control chromosomes in the GnomAD database, including 516 homozygotes. There are 3,324 hemizygotes in GnomAD. 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 0.10 (516 hom., 3324 hem., cov: 22)
• Consequence: CD40LG NM_000074.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.617

Genes affected

CD40LG (HGNC:11935): (CD40 ligand) The protein encoded by this gene is expressed on the surface of T cells. It regulates B cell function by engaging CD40 on the B cell surface. A defect in this gene results in an inability to undergo immunoglobulin class switch and is associated with hyper-IgM syndrome. [provided by RefSeq, Jul 2008]

CD40LG (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD40LG	NM_000074.3	c.346+628G>A		intron_variant		ENST00000370629.7	NP_000065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD40LG	ENST00000370629.7	c.346+628G>A		intron_variant		1	NM_000074.3	ENSP00000359663.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 11491 AN: 110797 Hom.: 512 Cov.: 22 AF XY: 0.100 AC XY: 3319 AN XY: 33065

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.0975

Gnomad ASJ AF: 0.122

Gnomad EAS AF: 0.0988

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0613

Gnomad MID AF: 0.164

Gnomad NFE AF: 0.0803

Gnomad OTH AF: 0.103

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.104 AC: 11505 AN: 110850 Hom.: 516 Cov.: 22 AF XY: 0.100 AC XY: 3324 AN XY: 33128

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0978

Gnomad4 ASJ AF: 0.122

Gnomad4 EAS AF: 0.0989

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.0613

Gnomad4 NFE AF: 0.0803

Gnomad4 OTH AF: 0.109

Alfa AF: 0.0903 Hom.: 2331

Bravo AF: 0.110

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.71

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

Other links and lift over

dbSNP: rs3092933; hg19: chrX-135737217;