GeneBe

rs6517532

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_033656.4(BRWD1):​c.1395+20G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

BRWD1
NM_033656.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.92

Publications

0 publications found
Variant links:
Genes affected
BRWD1 (HGNC:12760): (bromodomain and WD repeat domain containing 1) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by gly-his and trp-asp (GH-WD) residues which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes including cell cycle progression, signal transduction, apoptosis, and gene regulation. This protein contains 2 bromodomains and multiple WD repeats. This gene is located within the Down syndrome region-2 on chromosome 21. Alternative splicing of this gene generates multiple transcript variants encoding distinct isoforms. In mouse, this gene encodes a nuclear protein that has a polyglutamine-containing region that functions as a transcriptional activation domain which may regulate chromatin remodelling and associates with a component of the SWI/SNF chromatin remodelling complex.[provided by RefSeq, Jun 2011]
BRWD1 Gene-Disease associations (from GenCC):
  • agammaglobulinemia
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • ciliary dyskinesia, primary, 51
    Inheritance: AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
  • primary ciliary dyskinesia
    Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRWD1NM_033656.4 linkc.1395+20G>T intron_variant Intron 14 of 40 ENST00000342449.8 NP_387505.1 Q9NSI6-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRWD1ENST00000342449.8 linkc.1395+20G>T intron_variant Intron 14 of 40 1 NM_033656.4 ENSP00000344333.3 Q9NSI6-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1368640
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
675168
African (AFR)
AF:
0.00
AC:
0
AN:
29678
American (AMR)
AF:
0.00
AC:
0
AN:
28858
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22788
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37106
South Asian (SAS)
AF:
0.00
AC:
0
AN:
70152
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51366
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5276
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1067306
Other (OTH)
AF:
0.00
AC:
0
AN:
56110
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.0030
DANN
Benign
0.36
PhyloP100
-1.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Other links and lift over

dbSNP: rs6517532; hg19: chr21-40642189; API