chrX-136648280-G-A
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM1BP4BP6_Very_StrongBS1BS2
The NM_000074.3(CD40LG):c.32G>A(p.Arg11Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000265 in 1,201,660 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 109 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00023 ( 0 hom., 10 hem., cov: 22)
Exomes 𝑓: 0.00027 ( 0 hom. 99 hem. )
Consequence
CD40LG
NM_000074.3 missense
NM_000074.3 missense
Scores
3
3
11
Clinical Significance
Conservation
PhyloP100: 4.20
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM1
?
In a chain CD40 ligand, membrane form (size 260) in uniprot entity CD40L_HUMAN there are 53 pathogenic changes around while only 16 benign (77%) in NM_000074.3
BP4
?
Computational evidence support a benign effect (MetaRNN=0.35679162).
BP6
?
Variant X-136648280-G-A is Benign according to our data. Variant chrX-136648280-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 746752.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chrX-136648280-G-A is described in Lovd as [Likely_benign].
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000234 (26/111040) while in subpopulation AMR AF= 0.00048 (5/10416). AF 95% confidence interval is 0.000234. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd at 10 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CD40LG | NM_000074.3 | c.32G>A | p.Arg11Gln | missense_variant | 1/5 | ENST00000370629.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CD40LG | ENST00000370629.7 | c.32G>A | p.Arg11Gln | missense_variant | 1/5 | 1 | NM_000074.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000234 AC: 26AN: 111040Hom.: 0 Cov.: 22 AF XY: 0.000301 AC XY: 10AN XY: 33270
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GnomAD3 exomes AF: 0.000147 AC: 27AN: 183218Hom.: 0 AF XY: 0.000192 AC XY: 13AN XY: 67738
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GnomAD4 exome AF: 0.000269 AC: 293AN: 1090620Hom.: 0 Cov.: 28 AF XY: 0.000278 AC XY: 99AN XY: 356284
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Hyper-IgM syndrome type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 27, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2024 | CD40LG: BP4, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Pathogenic
DEOGEN2
Uncertain
D;T
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
REVEL
Uncertain
Sift
Pathogenic
D;D
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at