Genetic Variant BRD9:p.Met406Val (chr5-878410-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001375861.1(BRD9):c.1366A>G(p.Met456Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000287 in 1,395,520 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

Frequency

Genomes: not found (cov: 38)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

BRD9
NM_001375861.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.44

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.077693254).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375861.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRD9	NM_023924.5	MANE Select	c.1216A>G	p.Met406Val	missense	Exon 11 of 16	NP_076413.3
BRD9	NM_001375861.1		c.1366A>G	p.Met456Val	missense	Exon 12 of 17	NP_001362790.1
BRD9	NM_001375862.1		c.1339A>G	p.Met447Val	missense	Exon 12 of 17	NP_001362791.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
BRD9	ENST00000467963.6	TSL:2 MANE Select	c.1216A>G	p.Met406Val	missense	Exon 11 of 16	ENSP00000419765.1
BRD9	ENST00000475706.5	TSL:1	n.250A>G		non_coding_transcript_exon	Exon 3 of 6
BRD9	ENST00000489816.5	TSL:1	n.*908A>G		non_coding_transcript_exon	Exon 11 of 17	ENSP00000419752.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000287

AC:

AN:

1395520

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694888

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32454

American (AMR)

AF:

0.00

AC:

AN:

42552

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25034

East Asian (EAS)

AF:

0.00

AC:

AN:

38380

South Asian (SAS)

AF:

0.00

AC:

AN:

83748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

0.00000377

AC:

AN:

1059824

Other (OTH)

AF:

0.00

AC:

AN:

57682

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.338

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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

5.4

(source)

DANN

Benign

0.63

DEOGEN2

Benign

0.072

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.84

M_CAP

Benign

0.0064

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

PhyloP100

1.4

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

REVEL

Benign

0.043

Sift

Benign

0.23

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.35

MutPred

0.23

Gain of sheet (P = 0.0477)

MVP

0.28

MPC

0.35

ClinPred

0.060

GERP RS

-1.6

Varity_R

0.052

gMVP

0.42

Mutation Taster

=96/4

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

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