rs3092929

Variant names:

• chrX-136656764-A-C
• rs3092929
• NM_000074.3:c.409+346A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000074.3(CD40LG):​c.409+346A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 110,927 control chromosomes in the GnomAD database, including 2,585 homozygotes. There are 6,162 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 0.19 (2585 hom., 6162 hem., cov: 22)
• Consequence: CD40LG NM_000074.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000074.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD40LG	NM_000074.3	MANE Select	c.409+346A>C		intron	N/A	NP_000065.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD40LG	ENST00000370629.7	TSL:1 MANE Select	c.409+346A>C		intron	N/A	ENSP00000359663.2
	CD40LG	ENST00000370628.2	TSL:1	c.347-2275A>C		intron	N/A	ENSP00000359662.2
	CD40LG	ENST00000695724.1		c.*27+346A>C		intron	N/A	ENSP00000512122.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 21519 AN: 110873 Hom.: 2582 Cov.: 22

Gnomad AFR AF: 0.447

Gnomad AMI AF: 0.00437

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.101

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.0677

Gnomad MID AF: 0.227

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.194 AC: 21553 AN: 110927 Hom.: 2585 Cov.: 22 AF XY: 0.186 AC XY: 6162 AN XY: 33193

African (AFR) AF: 0.447 AC: 13521 AN: 30273

American (AMR) AF: 0.143 AC: 1506 AN: 10522

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 362 AN: 2629

East Asian (EAS) AF: 0.101 AC: 357 AN: 3521

South Asian (SAS) AF: 0.232 AC: 605 AN: 2608

European-Finnish (FIN) AF: 0.0677 AC: 409 AN: 6040

Middle Eastern (MID) AF: 0.235 AC: 51 AN: 217

European-Non Finnish (NFE) AF: 0.0843 AC: 4462 AN: 52907

Other (OTH) AF: 0.182 AC: 277 AN: 1524

Alfa AF: 0.165 Hom.: 1358

Bravo AF: 0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.4
DANN	Benign	0.66
PhyloP100		-0.13
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: rs3092929; hg19: chrX-135738923;