Variant rs3092923 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000074.3(CD40LG):c.410-13T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 1,206,594 control chromosomes in the GnomAD database, including 15,267 homozygotes. There are 50,475 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5848 hom., 8327 hem., cov: 22)

Exomes 𝑓: 0.12 ( 9419 hom. 42148 hem. )

Consequence

CD40LG
NM_000074.3 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.331

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant X-136659026-T-C is Benign according to our data. Variant chrX-136659026-T-C is described in ClinVar as [Benign]. Clinvar id is 518407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136659026-T-C is described in Lovd as [Benign]. Variant chrX-136659026-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CD40LG	NM_000074.3 linkuse as main transcript	c.410-13T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000370629.7	NP_000065.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CD40LG	ENST00000370629.7 linkuse as main transcript	c.410-13T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000074.3	ENSP00000359663	P1

Frequencies

GnomAD3 genomes

AF:

0.267

AC:

29594

AN:

110768

Hom.:

5844

Cov.:

AF XY:

0.249

AC XY:

8278

AN XY:

33294

show subpopulations

Gnomad AFR

AF:

0.697

Gnomad AMI

AF:

0.00438

Gnomad AMR

AF:

0.178

Gnomad ASJ

AF:

0.138

Gnomad EAS

AF:

0.101

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.0652

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.0858

Gnomad OTH

AF:

0.240

GnomAD3 exomes

AF:

0.167

AC:

30241

AN:

181473

Hom.:

3469

AF XY:

0.156

AC XY:

10442

AN XY:

66869

show subpopulations

Gnomad AFR exome

AF:

0.715

Gnomad AMR exome

AF:

0.180

Gnomad ASJ exome

AF:

0.128

Gnomad EAS exome

AF:

0.104

Gnomad SAS exome

AF:

0.248

Gnomad FIN exome

AF:

0.0745

Gnomad NFE exome

AF:

0.0901

Gnomad OTH exome

AF:

0.154

GnomAD4 exome

AF:

0.116

AC:

126805

AN:

1095772

Hom.:

9419

Cov.:

AF XY:

0.117

AC XY:

42148

AN XY:

361532

show subpopulations

Gnomad4 AFR exome

AF:

0.726

Gnomad4 AMR exome

AF:

0.182

Gnomad4 ASJ exome

AF:

0.128

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.234

Gnomad4 FIN exome

AF:

0.0755

Gnomad4 NFE exome

AF:

0.0852

Gnomad4 OTH exome

AF:

0.154

GnomAD4 genome

AF:

0.268

AC:

29654

AN:

110822

Hom.:

5848

Cov.:

AF XY:

0.250

AC XY:

8327

AN XY:

33360

show subpopulations

Gnomad4 AFR

AF:

0.697

Gnomad4 AMR

AF:

0.178

Gnomad4 ASJ

AF:

0.138

Gnomad4 EAS

AF:

0.101

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.0652

Gnomad4 NFE

AF:

0.0858

Gnomad4 OTH

AF:

0.244

Alfa

AF:

0.187

Hom.:

2122

Bravo

AF:

0.298

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Hyper-IgM syndrome type 1

Benign:2

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 21% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.1

DANN

Benign

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over