chr16-50320690-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_013263.5(BRD7):​c.1585G>A​(p.Val529Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,016 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

BRD7
NM_013263.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0890
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.016112775).
BS2
High AC in GnomAd4 at 10 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
BRD7NM_013263.5 linkc.1585G>A p.Val529Ile missense_variant Exon 14 of 17 ENST00000394688.8 NP_037395.2 Q9NPI1-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
BRD7ENST00000394688.8 linkc.1585G>A p.Val529Ile missense_variant Exon 14 of 17 1 NM_013263.5 ENSP00000378180.3 Q9NPI1-1
BRD7ENST00000394689.2 linkc.1588G>A p.Val530Ile missense_variant Exon 14 of 17 1 ENSP00000378181.2 Q9NPI1-2
BRD7ENST00000710357.1 linkc.1708G>A p.Val570Ile missense_variant Exon 14 of 17 ENSP00000518228.1
BRD7ENST00000710356.1 linkc.1636G>A p.Val546Ile missense_variant Exon 14 of 17 ENSP00000518227.1

Frequencies

GnomAD3 genomes
AF:
0.0000657
AC:
10
AN:
152170
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000517
AC:
13
AN:
251476
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000294
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000264
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000322
AC:
47
AN:
1461728
Hom.:
0
Cov.:
31
AF XY:
0.0000303
AC XY:
22
AN XY:
727182
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000151
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000243
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.0000657
AC:
10
AN:
152288
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000282
Hom.:
0
Bravo
AF:
0.0000567
ExAC
AF:
0.0000494
AC:
6
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 29, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1588G>A (p.V530I) alteration is located in exon 14 (coding exon 14) of the BRD7 gene. This alteration results from a G to A substitution at nucleotide position 1588, causing the valine (V) at amino acid position 530 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.062
BayesDel_addAF
Benign
-0.55
T
BayesDel_noAF
Benign
-0.72
CADD
Benign
1.9
DANN
Benign
0.66
DEOGEN2
Benign
0.019
T;.
Eigen
Benign
-1.3
Eigen_PC
Benign
-1.2
FATHMM_MKL
Benign
0.055
N
LIST_S2
Benign
0.35
T;T
M_CAP
Benign
0.0052
T
MetaRNN
Benign
0.016
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.0
N;.
PrimateAI
Benign
0.24
T
PROVEAN
Benign
0.12
N;N
REVEL
Benign
0.018
Sift
Benign
1.0
T;T
Sift4G
Benign
0.67
T;T
Polyphen
0.0
B;B
Vest4
0.074
MutPred
0.35
Loss of sheet (P = 0.0817);.;
MVP
0.20
MPC
0.11
ClinPred
0.0094
T
GERP RS
2.7
Varity_R
0.013
gMVP
0.093

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs555245080; hg19: chr16-50354601; COSMIC: COSV54266287; COSMIC: COSV54266287; API