Genetic Variant BRDT:c.-228G>C (chr1-91949492-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_207189.4(BRDT):c.-228G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.293 in 152,142 control chromosomes in the GnomAD database, including 7,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.29 ( 7718 hom., cov: 33)

Exomes 𝑓: 0.30 ( 1 hom. )

Consequence

BRDT
NM_207189.4 5_prime_UTR

Scores

Splicing: ADA: 0.00002108

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.58

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

spermatogenic failure 21
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

BRDT links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRDT	NM_207189.4 link	c.-228G>C		5_prime_UTR_variant	Exon 1 of 19	ENST00000399546.7	NP_997072.2	Q58F21-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRDT	ENST00000399546.7 link	c.-228G>C		5_prime_UTR_variant	Exon 1 of 19	2	NM_207189.4	ENSP00000387822.3		Q58F21-1

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44443

AN:

152004

Hom.:

7682

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.111

Gnomad AMR

AF:

0.251

Gnomad ASJ

AF:

0.149

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.153

Gnomad MID

AF:

0.180

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.292

GnomAD4 exome

AF:

0.300

AC:

AN:

Hom.:

Cov.:

AF XY:

0.278

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.278

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.293

AC:

44524

AN:

152122

Hom.:

7718

Cov.:

AF XY:

0.288

AC XY:

21423

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.488

AC:

20233

AN:

41470

American (AMR)

AF:

0.251

AC:

3835

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.149

AC:

517

AN:

3472

East Asian (EAS)

AF:

0.403

AC:

2082

AN:

5162

South Asian (SAS)

AF:

0.235

AC:

1131

AN:

4820

European-Finnish (FIN)

AF:

0.153

AC:

1619

AN:

10600

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.211

AC:

14330

AN:

68000

Other (OTH)

AF:

0.297

AC:

627

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1510

3020

4529

6039

7549

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.242

Hom.:

656

Bravo

AF:

0.309

Asia WGS

AF:

0.319

AC:

1111

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.1

(source)

DANN

Benign

0.44

PhyloP100

-1.6

PromoterAI

0.028

Neutral

(source)

Mutation Taster

=298/2

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000021

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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1-91949492-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over