dbSNP rs1126535: CD40LG:p.Leu50Leu (chrX-136648396-T-C) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000074.3(CD40LG):c.148T>C(p.Leu50Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,207,132 control chromosomes in the GnomAD database, including 17,805 homozygotes. There are 78,582 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.19 ( 1547 hom., 6545 hem., cov: 22)

Exomes 𝑓: 0.20 ( 16258 hom. 72037 hem. )

Consequence

CD40LG
NM_000074.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.309

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.61).

BP6

Variant X-136648396-T-C is Benign according to our data. Variant chrX-136648396-T-C is described in ClinVar as [Benign]. Clinvar id is 518406.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136648396-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.309 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.36 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD40LG	NM_000074.3 link	c.148T>C	p.Leu50Leu	synonymous_variant	Exon 1 of 5	ENST00000370629.7	NP_000065.1	P29965

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CD40LG	ENST00000370629.7 link	c.148T>C	p.Leu50Leu	synonymous_variant	Exon 1 of 5	1	NM_000074.3	ENSP00000359663.2		P29965

Frequencies

GnomAD3 genomes

AF:

0.189

AC:

21030

AN:

111467

Hom.:

1543

Cov.:

AF XY:

0.193

AC XY:

6535

AN XY:

33913

show subpopulations

Gnomad AFR

AF:

0.153

Gnomad AMI

AF:

0.0539

Gnomad AMR

AF:

0.369

Gnomad ASJ

AF:

0.150

Gnomad EAS

AF:

0.0861

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.208

GnomAD3 exomes

AF:

0.239

AC:

43636

AN:

182396

Hom.:

4641

AF XY:

0.233

AC XY:

15625

AN XY:

67200

show subpopulations

Gnomad AFR exome

AF:

0.153

Gnomad AMR exome

AF:

0.507

Gnomad ASJ exome

AF:

0.149

Gnomad EAS exome

AF:

0.0874

Gnomad SAS exome

AF:

0.338

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.224

GnomAD4 exome

AF:

0.197

AC:

216125

AN:

1095610

Hom.:

16258

Cov.:

AF XY:

0.199

AC XY:

72037

AN XY:

361642

show subpopulations

Gnomad4 AFR exome

AF:

0.148

Gnomad4 AMR exome

AF:

0.498

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.328

Gnomad4 FIN exome

AF:

0.202

Gnomad4 NFE exome

AF:

0.182

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.189

AC:

21047

AN:

111522

Hom.:

1547

Cov.:

AF XY:

0.193

AC XY:

6545

AN XY:

33978

show subpopulations

Gnomad4 AFR

AF:

0.153

Gnomad4 AMR

AF:

0.370

Gnomad4 ASJ

AF:

0.150

Gnomad4 EAS

AF:

0.0864

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.188

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.213

Alfa

AF:

0.185

Hom.:

12265

Bravo

AF:

0.204

EpiCase

AF:

0.176

EpiControl

AF:

0.171

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 61% of patients studied by a panel of primary immunodeficiencies. Number of patients: 58. Only high quality variants are reported. -

Hyper-IgM syndrome type 1

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

4.5

DANN

Benign

0.78

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

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