rs715762

Variant names:

• chrX-136651254-C-T
• rs715762
• NM_000074.3:c.288+857C>T

Variant summary

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

The NM_000074.3(CD40LG):​c.288+857C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0914 in 110,924 control chromosomes in the GnomAD database, including 514 homozygotes. There are 3,122 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 0.091 (514 hom., 3122 hem., cov: 22)
• Consequence: CD40LG NM_000074.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.114
• Publications: 2 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.261 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD40LG	NM_000074.3	c.288+857C>T		intron_variant	Intron 2 of 4	ENST00000370629.7	NP_000065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD40LG	ENST00000370629.7	c.288+857C>T		intron_variant	Intron 2 of 4	1	NM_000074.3	ENSP00000359663.2

Frequencies

GnomAD3 genomes AF: 0.0914 AC: 10129 AN: 110868 Hom.: 511 Cov.: 22

Gnomad AFR AF: 0.0204

Gnomad AMI AF: 0.0469

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.0855

Gnomad EAS AF: 0.00198

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.121

Gnomad MID AF: 0.0466

Gnomad NFE AF: 0.0975

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.0914 AC: 10135 AN: 110924 Hom.: 514 Cov.: 22 AF XY: 0.0942 AC XY: 3122 AN XY: 33148

African (AFR) AF: 0.0203 AC: 623 AN: 30615

American (AMR) AF: 0.269 AC: 2799 AN: 10404

Ashkenazi Jewish (ASJ) AF: 0.0855 AC: 225 AN: 2631

East Asian (EAS) AF: 0.00199 AC: 7 AN: 3522

South Asian (SAS) AF: 0.155 AC: 397 AN: 2555

European-Finnish (FIN) AF: 0.121 AC: 713 AN: 5913

Middle Eastern (MID) AF: 0.0465 AC: 10 AN: 215

European-Non Finnish (NFE) AF: 0.0975 AC: 5157 AN: 52878

Other (OTH) AF: 0.114 AC: 172 AN: 1509

Alfa AF: 0.0932 Hom.: 531

Bravo AF: 0.104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.9
DANN	Benign	0.57
PhyloP100		0.11
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: rs715762; hg19: chrX-135733413;