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GeneBe

17-75846959-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_012478.4(WBP2):c.681C>T(p.Ala227=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00601 in 1,614,114 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 106 hom., cov: 32)
Exomes 𝑓: 0.0043 ( 136 hom. )

Consequence

WBP2
NM_012478.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.785
Variant links:
Genes affected
WBP2 (HGNC:12738): (WW domain binding protein 2) The globular WW domain is composed of 38 to 40 semiconserved amino acids shared by proteins of diverse functions including structural, regulatory, and signaling proteins. The domain is involved in mediating protein-protein interactions through the binding of polyproline ligands. This gene encodes a WW domain binding protein that is a transcriptional coactivator of estrogen receptor alpha and progesterone receptor. Defects in this gene have been associated with hearing impairment. [provided by RefSeq, Jan 2017]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 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=-0.44).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-75846959-G-A is Benign according to our data. Variant chr17-75846959-G-A is described in ClinVar as [Benign]. Clinvar id is 1243088.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
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=0.785 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.065 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WBP2NM_012478.4 linkuse as main transcriptc.681C>T p.Ala227= synonymous_variant 7/8 ENST00000254806.8
WBP2NM_001348170.1 linkuse as main transcriptc.681C>T p.Ala227= synonymous_variant 8/9
WBP2NM_001330499.2 linkuse as main transcriptc.546C>T p.Ala182= synonymous_variant 6/7
WBP2XM_047435712.1 linkuse as main transcriptc.615C>T p.Ala205= synonymous_variant 7/8

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WBP2ENST00000254806.8 linkuse as main transcriptc.681C>T p.Ala227= synonymous_variant 7/81 NM_012478.4 P4Q969T9-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0222
AC:
3383
AN:
152154
Hom.:
106
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0672
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0202
Gnomad ASJ
AF:
0.00288
Gnomad EAS
AF:
0.0241
Gnomad SAS
AF:
0.0149
Gnomad FIN
AF:
0.000565
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000559
Gnomad OTH
AF:
0.0196
GnomAD3 exomes
AF:
0.0129
AC:
3231
AN:
251138
Hom.:
76
AF XY:
0.0109
AC XY:
1479
AN XY:
135826
show subpopulations
Gnomad AFR exome
AF:
0.0712
Gnomad AMR exome
AF:
0.0306
Gnomad ASJ exome
AF:
0.00189
Gnomad EAS exome
AF:
0.0232
Gnomad SAS exome
AF:
0.0142
Gnomad FIN exome
AF:
0.000786
Gnomad NFE exome
AF:
0.000643
Gnomad OTH exome
AF:
0.00734
GnomAD4 exome
AF:
0.00431
AC:
6307
AN:
1461842
Hom.:
136
Cov.:
32
AF XY:
0.00429
AC XY:
3122
AN XY:
727224
show subpopulations
Gnomad4 AFR exome
AF:
0.0657
Gnomad4 AMR exome
AF:
0.0302
Gnomad4 ASJ exome
AF:
0.00241
Gnomad4 EAS exome
AF:
0.0163
Gnomad4 SAS exome
AF:
0.0133
Gnomad4 FIN exome
AF:
0.000974
Gnomad4 NFE exome
AF:
0.000290
Gnomad4 OTH exome
AF:
0.00833
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0223
AC:
3389
AN:
152272
Hom.:
106
Cov.:
32
AF XY:
0.0219
AC XY:
1631
AN XY:
74448
show subpopulations
Gnomad4 AFR
AF:
0.0671
Gnomad4 AMR
AF:
0.0200
Gnomad4 ASJ
AF:
0.00288
Gnomad4 EAS
AF:
0.0242
Gnomad4 SAS
AF:
0.0152
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.000559
Gnomad4 OTH
AF:
0.0199
Alfa
AF:
0.0112
Hom.:
28
Bravo
AF:
0.0263
Asia WGS
AF:
0.0230
AC:
79
AN:
3478
EpiCase
AF:
0.000600
EpiControl
AF:
0.000593

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitterclinical testingGeneDxMay 05, 2021- -
Benign, criteria provided, single submitterclinical testingInvitaeJan 18, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.44
Cadd
Benign
9.6
Dann
Benign
0.93
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs35171947; hg19: chr17-73843040; API