rs5930973

Positions:

• chrX-136649989-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000074.3(CD40LG):​c.157-277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0379 in 112,392 control chromosomes in the GnomAD database, including 92 homozygotes. There are 1,161 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.038 (92 hom., 1161 hem., cov: 23)
• Consequence: CD40LG NM_000074.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.142

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant X-136649989-G-A is Benign according to our data. Variant chrX-136649989-G-A is described in ClinVar as [Benign]. Clinvar id is 1282887.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD40LG	NM_000074.3	c.157-277G>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.157-277G>A		intron_variant		1	NM_000074.3	ENSP00000359663	P1

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 4256 AN: 112337 Hom.: 92 Cov.: 23 AF XY: 0.0336 AC XY: 1160 AN XY: 34521

Gnomad AFR AF: 0.00843

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0211

Gnomad ASJ AF: 0.0208

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00289

Gnomad FIN AF: 0.0472

Gnomad MID AF: 0.00418

Gnomad NFE AF: 0.0631

Gnomad OTH AF: 0.0317

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

GnomAD4 genome AF: 0.0379 AC: 4256 AN: 112392 Hom.: 92 Cov.: 23 AF XY: 0.0336 AC XY: 1161 AN XY: 34586

Gnomad4 AFR AF: 0.00841

Gnomad4 AMR AF: 0.0210

Gnomad4 ASJ AF: 0.0208

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00327

Gnomad4 FIN AF: 0.0472

Gnomad4 NFE AF: 0.0631

Gnomad4 OTH AF: 0.0314

Alfa AF: 0.0530 Hom.: 974

Bravo AF: 0.0355

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.19
DANN	Benign	0.54

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: rs5930973; hg19: chrX-135732148;