22-49776154-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001304808.3(BRD1):​c.3127G>A​(p.Gly1043Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000561 in 1,604,112 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G1043A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

BRD1
NM_001304808.3 missense

Scores

5
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.70
Variant links:
Genes affected
BRD1 (HGNC:1102): (bromodomain containing 1) This gene encodes a bromodomain-containing protein that localizes to the nucleus and can interact with DNA and histone tails. The encoded protein is a component of the MOZ/MORF acetyltransferase complex and can stimulate acetylation of histones H3 and H4, thereby potentially playing a role in gene activation. Variation in this gene is associated with schizophrenia and bipolar disorder in some study populations. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRD1NM_001304808.3 linkc.3127G>A p.Gly1043Ser missense_variant Exon 11 of 13 ENST00000404760.6 NP_001291737.1 O95696-2A0A024R4V5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRD1ENST00000404760.6 linkc.3127G>A p.Gly1043Ser missense_variant Exon 11 of 13 2 NM_001304808.3 ENSP00000385858.1 O95696-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152074
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
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
GnomAD3 exomes
AF:
0.00000837
AC:
2
AN:
238896
Hom.:
0
AF XY:
0.00000767
AC XY:
1
AN XY:
130438
show subpopulations
Gnomad AFR exome
AF:
0.0000633
Gnomad AMR exome
AF:
0.0000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000344
AC:
5
AN:
1452038
Hom.:
0
Cov.:
33
AF XY:
0.00000415
AC XY:
3
AN XY:
722708
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000332
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152074
Hom.:
0
Cov.:
33
AF XY:
0.0000404
AC XY:
3
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000642
ESP6500AA
AF:
0.000227
AC:
1
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000165
AC:
2

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 23, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.2734G>A (p.G912S) alteration is located in exon 10 (coding exon 10) of the BRD1 gene. This alteration results from a G to A substitution at nucleotide position 2734, causing the glycine (G) at amino acid position 912 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.084
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Benign
0.93
DEOGEN2
Benign
0.064
T;T;.;.
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.12
FATHMM_MKL
Uncertain
0.86
D
LIST_S2
Benign
0.86
.;D;.;D
M_CAP
Benign
0.025
D
MetaRNN
Uncertain
0.63
D;D;D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;M;.;.
PrimateAI
Uncertain
0.75
T
PROVEAN
Benign
-1.2
N;N;N;.
REVEL
Benign
0.16
Sift
Benign
0.045
D;D;D;.
Sift4G
Benign
0.14
T;T;T;T
Polyphen
0.99
D;D;D;D
Vest4
0.63
MVP
0.52
MPC
0.49
ClinPred
0.21
T
GERP RS
4.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.17
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs147405126; hg19: chr22-50169802; API