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GeneBe

X-136648287-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_000074.3(CD40LG):c.39G>A(p.Ala13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000317 in 1,200,025 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., 0 hem., cov: 22)
Exomes 𝑓: 0.000028 ( 0 hom. 15 hem. )

Consequence

CD40LG
NM_000074.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.811
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant X-136648287-G-A is Benign according to our data. Variant chrX-136648287-G-A is described in ClinVar as [Benign]. Clinvar id is 1169681.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chrX-136648287-G-A is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.811 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000072 (8/111092) while in subpopulation AMR AF= 0.000287 (3/10443). AF 95% confidence interval is 0.0000777. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Hemizygotes in GnomAdExome at 5 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CD40LGNM_000074.3 linkuse as main transcriptc.39G>A p.Ala13= synonymous_variant 1/5 ENST00000370629.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CD40LGENST00000370629.7 linkuse as main transcriptc.39G>A p.Ala13= synonymous_variant 1/51 NM_000074.3 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000720
AC:
8
AN:
111092
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33334
show subpopulations
Gnomad AFR
AF:
0.0000655
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000287
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000377
Gnomad OTH
AF:
0.000673
GnomAD3 exomes
AF:
0.0000437
AC:
8
AN:
183221
Hom.:
0
AF XY:
0.0000738
AC XY:
5
AN XY:
67749
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000730
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000723
Gnomad SAS exome
AF:
0.0000524
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000367
Gnomad OTH exome
AF:
0.000221
GnomAD4 exome
AF:
0.0000275
AC:
30
AN:
1088933
Hom.:
0
Cov.:
28
AF XY:
0.0000423
AC XY:
15
AN XY:
354619
show subpopulations
Gnomad4 AFR exome
AF:
0.0000381
Gnomad4 AMR exome
AF:
0.0000568
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000332
Gnomad4 SAS exome
AF:
0.0000927
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000240
Gnomad4 OTH exome
AF:
0.0000218
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0000720
AC:
8
AN:
111092
Hom.:
0
Cov.:
22
AF XY:
0.00
AC XY:
0
AN XY:
33334
show subpopulations
Gnomad4 AFR
AF:
0.0000655
Gnomad4 AMR
AF:
0.000287
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000377
Gnomad4 OTH
AF:
0.000673
Bravo
AF:
0.0000567

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hyper-IgM syndrome type 1 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 31, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
5.0
Dann
Benign
0.39

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.

Other links and lift over

dbSNP: rs779460863; hg19: chrX-135730446; API