rs797045419
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6BP7
The NM_153252.5(BRWD3):c.3690A>G(p.Ala1230Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,095,491 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000027 ( 0 hom. 0 hem. )
Consequence
BRWD3
NM_153252.5 synonymous
NM_153252.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.12
Publications
0 publications found
Genes affected
BRWD3 (HGNC:17342): (bromodomain and WD repeat domain containing 3) The protein encoded by this gene contains a bromodomain and several WD repeats. It is thought to have a chromatin-modifying function, and may thus play a role in transcription. Mutations in this gene are associated with a spectrum of cognitive disabilities and X-linked macrocephaly. This gene is also associated with translocations in patients with B-cell chronic lymphocytic leukemia. [provided by RefSeq, Jul 2017]
BRWD3 Gene-Disease associations (from GenCC):
- intellectual disability, X-linked 93Inheritance: XL, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- X-linked syndromic intellectual disabilityInheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
- infantile spasmsInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- self-limited epilepsy with centrotemporal spikesInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.49).
BP6
Variant X-80690005-T-C is Benign according to our data. Variant chrX-80690005-T-C is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 210541.
BP7
Synonymous conserved (PhyloP=1.12 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_153252.5. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BRWD3 | NM_153252.5 | MANE Select | c.3690A>G | p.Ala1230Ala | synonymous | Exon 32 of 41 | NP_694984.5 | ||
| BRWD3 | NM_001441339.1 | c.3540A>G | p.Ala1180Ala | synonymous | Exon 31 of 40 | NP_001428268.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| BRWD3 | ENST00000373275.5 | TSL:1 MANE Select | c.3690A>G | p.Ala1230Ala | synonymous | Exon 32 of 41 | ENSP00000362372.4 | ||
| BRWD3 | ENST00000473691.1 | TSL:2 | n.1826A>G | non_coding_transcript_exon | Exon 16 of 25 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
22
GnomAD2 exomes AF: 0.0000110 AC: 2AN: 182604 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
182604
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000274 AC: 3AN: 1095491Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 361387 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1095491
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
361387
show subpopulations
African (AFR)
AF:
AC:
0
AN:
26348
American (AMR)
AF:
AC:
2
AN:
35143
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
19324
East Asian (EAS)
AF:
AC:
1
AN:
30128
South Asian (SAS)
AF:
AC:
0
AN:
53929
European-Finnish (FIN)
AF:
AC:
0
AN:
40448
Middle Eastern (MID)
AF:
AC:
0
AN:
4128
European-Non Finnish (NFE)
AF:
AC:
0
AN:
840077
Other (OTH)
AF:
AC:
0
AN:
45966
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.542
Heterozygous variant carriers
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0
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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GnomAD4 genome
GnomAD4 genome
Cov.:
22
Alfa
AF:
Hom.:
Bravo
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ClinVar
ClinVar submissions as Germline
Significance:Conflicting classifications of pathogenicity
Revision:criteria provided, conflicting classifications
Pathogenic
VUS
Benign
Condition
-
-
1
not provided (1)
-
1
-
not specified (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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