rs508016

Variant names:

• chr5-878410-T-A
• rs508016
• NM_023924.5:c.1216A>T

Your query was ambiguous. Multiple possible variants found:

• chr5-878410-T-A
• chr5-878410-T-C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_023924.5(BRD9):​c.1216A>T​(p.Met406Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.32 (0 hom., cov: 38)
  • Exomes 𝑓: 0.36 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: BRD9 NM_023924.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 20 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0016848445).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD9	NM_023924.5	MANE Select	c.1216A>T	p.Met406Leu	missense	Exon 11 of 16	NP_076413.3
	BRD9	NM_001375861.1		c.1366A>T	p.Met456Leu	missense	Exon 12 of 17	NP_001362790.1
	BRD9	NM_001375862.1		c.1339A>T	p.Met447Leu	missense	Exon 12 of 17	NP_001362791.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRD9	ENST00000467963.6	TSL:2 MANE Select	c.1216A>T	p.Met406Leu	missense	Exon 11 of 16	ENSP00000419765.1
	BRD9	ENST00000475706.5	TSL:1	n.250A>T		non_coding_transcript_exon	Exon 3 of 6
	BRD9	ENST00000489816.5	TSL:1	n.*908A>T		non_coding_transcript_exon	Exon 11 of 17	ENSP00000419752.1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 31782 AN: 98106 Hom.: 0 Cov.: 38

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.345

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.298

Gnomad EAS AF: 0.369

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.334

GnomAD2 exomes AF: 0.319 AC: 47674 AN: 149386 AF XY: 0.314

Gnomad AFR exome AF: 0.380

Gnomad AMR exome AF: 0.331

Gnomad ASJ exome AF: 0.282

Gnomad EAS exome AF: 0.391

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.297

Gnomad OTH exome AF: 0.326

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.356 AC: 334100 AN: 938912 Hom.: 0 Cov.: 82 AF XY: 0.353 AC XY: 164733 AN XY: 466496

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

African (AFR) AF: 0.400 AC: 9862 AN: 24638

American (AMR) AF: 0.345 AC: 9098 AN: 26408

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 5131 AN: 15686

East Asian (EAS) AF: 0.403 AC: 10330 AN: 25610

South Asian (SAS) AF: 0.331 AC: 17745 AN: 53648

European-Finnish (FIN) AF: 0.345 AC: 12588 AN: 36520

Middle Eastern (MID) AF: 0.353 AC: 1312 AN: 3714

European-Non Finnish (NFE) AF: 0.356 AC: 254366 AN: 714014

Other (OTH) AF: 0.353 AC: 13668 AN: 38674

⚠️ 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.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.324 AC: 31818 AN: 98180 Hom.: 0 Cov.: 38 AF XY: 0.325 AC XY: 15699 AN XY: 48262

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

African (AFR) AF: 0.351 AC: 10253 AN: 29206

American (AMR) AF: 0.318 AC: 2936 AN: 9224

Ashkenazi Jewish (ASJ) AF: 0.298 AC: 595 AN: 1996

East Asian (EAS) AF: 0.370 AC: 1147 AN: 3102

South Asian (SAS) AF: 0.310 AC: 919 AN: 2966

European-Finnish (FIN) AF: 0.334 AC: 2282 AN: 6824

Middle Eastern (MID) AF: 0.285 AC: 53 AN: 186

European-Non Finnish (NFE) AF: 0.304 AC: 12954 AN: 42668

Other (OTH) AF: 0.335 AC: 478 AN: 1426

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.324 Hom.: 7

ExAC AF: 0.358 AC: 43492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Benign	0.85
DEOGEN2	Benign	0.076	T
Eigen	Benign	-0.84
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.66	D
LIST_S2	Uncertain	0.93	D
MetaRNN	Benign	0.0017	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L
PhyloP100		1.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.060
Sift	Benign	0.087	T
Sift4G	Benign	0.40	T
Polyphen		0.0060	B
Vest4		0.38
MutPred		0.30		Loss of sheet (P = 0.0315)
MPC		0.32
ClinPred		0.0062	T
GERP RS		-1.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.089
gMVP		0.45
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs508016; hg19: chr5-878525; COSMIC: COSV60244448; COSMIC: COSV60244448;