rs3092933

Variant names:

• chrX-136655058-G-A
• rs3092933
• NM_000074.3:c.346+628G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• hyper-IgM syndrome type 1

  Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CD40LG	NM_000074.3	c.346+628G>A		intron_variant	Intron 3 of 4	ENST00000370629.7	NP_000065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD40LG	ENST00000370629.7	c.346+628G>A		intron_variant	Intron 3 of 4	1	NM_000074.3	ENSP00000359663.2

Frequencies

GnomAD3 genomes AF: 0.104 AC: 11491 AN: 110797 Hom.: 512 Cov.: 22

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

African (AFR) AF: 0.147 AC: 4478 AN: 30430

American (AMR) AF: 0.0978 AC: 1024 AN: 10470

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 323 AN: 2639

East Asian (EAS) AF: 0.0989 AC: 348 AN: 3519

South Asian (SAS) AF: 0.203 AC: 520 AN: 2559

European-Finnish (FIN) AF: 0.0613 AC: 365 AN: 5955

Middle Eastern (MID) AF: 0.171 AC: 37 AN: 217

European-Non Finnish (NFE) AF: 0.0803 AC: 4243 AN: 52869

Other (OTH) AF: 0.109 AC: 164 AN: 1509

Alfa AF: 0.0903 Hom.: 2504

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
PhyloP100		0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs3092933; hg19: chrX-135737217;