X-48683512-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The ENST00000698625.1(WAS):​c.-34-308T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0143 in 204,149 control chromosomes in the GnomAD database, including 91 homozygotes. There are 723 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.023 ( 79 hom., 681 hem., cov: 22)
Exomes 𝑓: 0.0035 ( 12 hom. 42 hem. )

Consequence

WAS
ENST00000698625.1 intron

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.177
Variant links:
Genes affected
WAS (HGNC:12731): (WASP actin nucleation promoting factor) The Wiskott-Aldrich syndrome (WAS) family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton. The presence of a number of different motifs suggests that they are regulated by a number of different stimuli, and interact with multiple proteins. Recent studies have demonstrated that these proteins, directly or indirectly, associate with the small GTPase, Cdc42, known to regulate formation of actin filaments, and the cytoskeletal organizing complex, Arp2/3. Wiskott-Aldrich syndrome is a rare, inherited, X-linked, recessive disease characterized by immune dysregulation and microthrombocytopenia, and is caused by mutations in the WAS gene. The WAS gene product is a cytoplasmic protein, expressed exclusively in hematopoietic cells, which show signalling and cytoskeletal abnormalities in WAS patients. A transcript variant arising as a result of alternative promoter usage, and containing a different 5' UTR sequence, has been described, however, its full-length nature is not known. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant X-48683512-T-C is Benign according to our data. Variant chrX-48683512-T-C is described in ClinVar as [Benign]. Clinvar id is 1265197.Status of the report is criteria_provided_single_submitter, 1 stars.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0782 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WASXM_011543977.3 linkuse as main transcriptc.-34-308T>C intron_variant
WASXM_017029786.2 linkuse as main transcriptc.-34-308T>C intron_variant
WASXM_047442432.1 linkuse as main transcriptc.-34-308T>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WASENST00000450772.5 linkuse as main transcriptc.-35+149T>C intron_variant 3
WASENST00000698625.1 linkuse as main transcriptc.-34-308T>C intron_variant P2

Frequencies

GnomAD3 genomes
AF:
0.0233
AC:
2605
AN:
111756
Hom.:
78
Cov.:
22
AF XY:
0.0201
AC XY:
681
AN XY:
33948
show subpopulations
Gnomad AFR
AF:
0.0810
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00845
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00110
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000226
Gnomad OTH
AF:
0.0152
GnomAD4 exome
AF:
0.00351
AC:
324
AN:
92342
Hom.:
12
AF XY:
0.00235
AC XY:
42
AN XY:
17866
show subpopulations
Gnomad4 AFR exome
AF:
0.0751
Gnomad4 AMR exome
AF:
0.00613
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000165
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000138
Gnomad4 OTH exome
AF:
0.00507
GnomAD4 genome
AF:
0.0233
AC:
2605
AN:
111807
Hom.:
79
Cov.:
22
AF XY:
0.0200
AC XY:
681
AN XY:
34009
show subpopulations
Gnomad4 AFR
AF:
0.0809
Gnomad4 AMR
AF:
0.00834
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000736
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000226
Gnomad4 OTH
AF:
0.0150
Alfa
AF:
0.00651
Hom.:
115
Bravo
AF:
0.0268

ClinVar

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

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxApr 25, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
4.1
DANN
Benign
0.84

Splicing

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: rs235422; hg19: chrX-48541901; API