16-50320765-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_013263.5(BRD7):c.1510G>A(p.Val504Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000067 in 1,612,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000067 (0 hom.)
• Consequence: BRD7 NM_013263.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.437

Genes affected

BRD7 (HGNC:14310): (bromodomain containing 7) This gene encodes a protein which is a member of the bromodomain-containing protein family. The product of this gene has been identified as a component of one form of the SWI/SNF chromatin remodeling complex, and as a protein which interacts with p53 and is required for p53-dependent oncogene-induced senescence which prevents tumor growth. Pseudogenes have been described on chromosomes 2, 3, 6, 13 and 14. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.019670427).
• BP6: Variant 16-50320765-C-T is Benign according to our data. Variant chr16-50320765-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2346164.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRD7	NM_013263.5	c.1510G>A	p.Val504Ile	missense_variant	14/17	ENST00000394688.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRD7	ENST00000394688.8	c.1510G>A	p.Val504Ile	missense_variant	14/17	1	NM_013263.5	P4
BRD7	ENST00000394689.2	c.1513G>A	p.Val505Ile	missense_variant	14/17	1		A1
BRD7	ENST00000710357.1	c.1633G>A	p.Val545Ile	missense_variant	14/17
BRD7	ENST00000710356.1	c.1561G>A	p.Val521Ile	missense_variant	14/17

Frequencies

GnomAD3 genomes AF: 0.0000657 AC: 10 AN: 152206 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000955 AC: 24 AN: 251338 Hom.: 0 AF XY: 0.0000957 AC XY: 13 AN XY: 135830

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.0000868

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000158

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000671 AC: 98 AN: 1460198 Hom.: 0 Cov.: 30 AF XY: 0.0000619 AC XY: 45 AN XY: 726550

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000671

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000374

Gnomad4 NFE exome AF: 0.0000765

Gnomad4 OTH exome AF: 0.0000995

GnomAD4 genome AF: 0.0000657 AC: 10 AN: 152206 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74360

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000134 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.000107 AC: 13

EpiCase AF: 0.000109

EpiControl AF: 0.000356

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	1.9
Dann	Benign	0.84
DEOGEN2	Benign	0.023	T;.
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0074	N
LIST_S2	Benign	0.26	T;T
M_CAP	Benign	0.0079	T
MetaRNN	Benign	0.020	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-0.69	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.23	N;N
REVEL	Benign	0.072
Sift	Benign	0.63	T;T
Sift4G	Benign	0.21	T;T
Polyphen		0.0	B;B
Vest4		0.10
MVP		0.20
MPC		0.11
ClinPred		0.014	T
GERP RS		-4.6
Varity_R		0.031
gMVP		0.059

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: rs201216846; hg19: chr16-50354676;