Variant 1-91977245-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The NM_207189.4(BRDT):c.821G>A(p.Arg274Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000286 in 1,614,042 control chromosomes in the GnomAD database, including 4 homozygotes. 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 (no stars).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00015 ( 1 hom. )

Consequence

BRDT
NM_207189.4 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.75

Variant links:

Genes affected

BRDT (HGNC:1105): (bromodomain testis associated) BRDT is similar to the RING3 protein family. It possesses 2 bromodomain motifs and a PEST sequence (a cluster of proline, glutamic acid, serine, and threonine residues), characteristic of proteins that undergo rapid intracellular degradation. The bromodomain is found in proteins that regulate transcription. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jun 2011]

BRDT links:

BRDT (HGNC:):

BRDT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00478673).

BP6

Variant 1-91977245-G-A is Benign according to our data. Variant chr1-91977245-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3050280.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRDT	NM_207189.4 linkuse as main transcript	c.821G>A	p.Arg274Lys	missense_variant	6/19	ENST00000399546.7	NP_997072.2	Q58F21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRDT	ENST00000399546.7 linkuse as main transcript	c.821G>A	p.Arg274Lys	missense_variant	6/19	2	NM_207189.4	ENSP00000387822.3		Q58F21-1

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

237

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00567

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000390

AC:

AN:

251066

Hom.:

AF XY:

0.000339

AC XY:

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.00578

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000150

AC:

219

AN:

1461728

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

101

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.00586

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.00159

AC:

242

AN:

152314

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00577

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000346

Hom.:

Bravo

AF:

0.00180

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000486

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

BRDT-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.8

DANN

Benign

0.39

DEOGEN2

Benign

0.077

T;.;.;.;T;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.51

.;T;T;T;T;T

M_CAP

Benign

0.0070

MetaRNN

Benign

0.0048

T;T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.055

N;.;.;.;.;N

PrimateAI

Benign

0.27

PROVEAN

Benign

1.5

N;N;N;.;N;N

REVEL

Benign

0.032

Sift

Benign

1.0

T;T;T;.;T;T

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0

B;.;.;.;.;B

Vest4

0.051

MVP

0.32

MPC

0.082

ClinPred

0.0033

GERP RS

1.1

Varity_R

0.037

gMVP

0.29

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over