Genetic Variant BRD9:p.Gly542Ser (chr5-865483-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_023924.5(BRD9):c.1624G>A(p.Gly542Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000162 in 1,602,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G542C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

BRD9
NM_023924.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.83

Publications

1 publications found

Variant links:

Genes affected

BRD9 (HGNC:25818): (bromodomain containing 9) Enables lysine-acetylated histone binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of SWI/SNF complex. [provided by Alliance of Genome Resources, Apr 2022]

BRD9 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.24740985).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023924.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRD9	NM_023924.5	MANE Select	c.1624G>A	p.Gly542Ser	missense	Exon 15 of 16	NP_076413.3	Q9H8M2-5
BRD9	NM_001375861.1		c.1774G>A	p.Gly592Ser	missense	Exon 16 of 17	NP_001362790.1
BRD9	NM_001375862.1		c.1747G>A	p.Gly583Ser	missense	Exon 16 of 17	NP_001362791.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRD9	ENST00000467963.6	TSL:2 MANE Select	c.1624G>A	p.Gly542Ser	missense	Exon 15 of 16	ENSP00000419765.1	Q9H8M2-5
BRD9	ENST00000489816.5	TSL:1	n.*1466G>A		non_coding_transcript_exon	Exon 16 of 17	ENSP00000419752.1	F2Z2E8
BRD9	ENST00000490814.6	TSL:1	n.*2262G>A		non_coding_transcript_exon	Exon 18 of 19	ENSP00000417431.2	F2Z2E8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.0000323

AC:

AN:

247976

AF XY:

0.0000447

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000172

AC:

AN:

1449838

Hom.:

Cov.:

AF XY:

0.0000278

AC XY:

AN XY:

719500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33350

American (AMR)

AF:

0.00

AC:

AN:

44576

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.0000254

AC:

AN:

39406

South Asian (SAS)

AF:

0.000232

AC:

AN:

86070

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48914

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00000271

AC:

AN:

1105726

Other (OTH)

AF:

0.0000167

AC:

AN:

59968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

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:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41454

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

Eigen

Uncertain

0.27

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.063

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.6

PhyloP100

6.8

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.32

REVEL

Benign

0.16

Sift

Uncertain

0.025

Sift4G

Benign

0.12

Polyphen

0.98

Vest4

0.42

MVP

0.38

MPC

0.78

ClinPred

0.24

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.42

Mutation Taster

=77/23

polymorphism

(source)

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

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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