chr5-878410-T-A

Variant names:

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

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. 15/22 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

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).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRD9	NM_023924.5	c.1216A>T	p.Met406Leu	missense_variant	Exon 11 of 16	ENST00000467963.6	NP_076413.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRD9	ENST00000467963.6	c.1216A>T	p.Met406Leu	missense_variant	Exon 11 of 16	2	NM_023924.5	ENSP00000419765.1

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

Gnomad4 AFR exome AF: 0.400 AC: 9862 AN: 24638

Gnomad4 AMR exome AF: 0.345 AC: 9098 AN: 26408

Gnomad4 ASJ exome AF: 0.327 AC: 5131 AN: 15686

Gnomad4 EAS exome AF: 0.403 AC: 10330 AN: 25610

Gnomad4 SAS exome AF: 0.331 AC: 17745 AN: 53648

Gnomad4 FIN exome AF: 0.345 AC: 12588 AN: 36520

Gnomad4 NFE exome AF: 0.356 AC: 254366 AN: 714014

Gnomad4 Remaining exome AF: 0.353 AC: 13668 AN: 38674

⚠️ The allele balance in gnomAD4 Exomes is highly skewed (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

Gnomad4 AFR AF: 0.351 AC: 0.351058 AN: 0.351058

Gnomad4 AMR AF: 0.318 AC: 0.3183 AN: 0.3183

Gnomad4 ASJ AF: 0.298 AC: 0.298096 AN: 0.298096

Gnomad4 EAS AF: 0.370 AC: 0.369761 AN: 0.369761

Gnomad4 SAS AF: 0.310 AC: 0.309845 AN: 0.309845

Gnomad4 FIN AF: 0.334 AC: 0.334408 AN: 0.334408

Gnomad4 NFE AF: 0.304 AC: 0.3036 AN: 0.3036

Gnomad4 OTH AF: 0.335 AC: 0.335203 AN: 0.335203

Alfa AF: 0.324 Hom.: 7

ExAC AF: 0.358 AC: 43492

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
MetaRNN	Benign	0.0017	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	.;L
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.060
Sift	Benign	0.087	T;T
Sift4G	Benign	0.40	T;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

Publications

LitVar

Other links and lift over

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