Genetic Variant NM_012478.4:c.655+11T>C (chr17-75847476-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_012478.4(WBP2):c.655+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000302 in 1,590,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

WBP2
NM_012478.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.581

Publications

0 publications found

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]

WBP2 Gene-Disease associations (from GenCC):

hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen
hearing loss, autosomal recessive 107
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

WBP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-75847476-A-G is Benign according to our data. Variant chr17-75847476-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1651591.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012478.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WBP2	NM_012478.4	MANE Select	c.655+11T>C	intron	N/A	NP_036610.2
WBP2	NM_001348170.1		c.655+11T>C	intron	N/A	NP_001335099.1	Q969T9-1
WBP2	NM_001330499.2		c.520+11T>C	intron	N/A	NP_001317428.1	Q969T9-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WBP2	ENST00000254806.8	TSL:1 MANE Select	c.655+11T>C	intron	N/A	ENSP00000254806.3	Q969T9-1
WBP2	ENST00000591399.5	TSL:5	c.655+11T>C	intron	N/A	ENSP00000467579.1	Q969T9-1
WBP2	ENST00000590221.5	TSL:3	c.643+11T>C	intron	N/A	ENSP00000466450.1	K7EMC9

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000936

AC:

AN:

213624

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.0000712

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000193

GnomAD4 exome

AF:

0.0000271

AC:

AN:

1438138

Hom.:

Cov.:

AF XY:

0.0000210

AC XY:

AN XY:

714356

show subpopulations

African (AFR)

AF:

0.000610

AC:

AN:

32804

American (AMR)

AF:

0.00

AC:

AN:

40414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24526

East Asian (EAS)

AF:

0.00

AC:

AN:

39250

South Asian (SAS)

AF:

0.00

AC:

AN:

82852

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51824

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101474

Other (OTH)

AF:

0.000320

AC:

AN:

59358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152252

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41536

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000453

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.62

PhyloP100

0.58

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over