rs10783071

Positions:

• chr1-91962938-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207189.4(BRDT):​c.184C>A​(p.Gln62Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.911 in 1,585,074 control chromosomes in the GnomAD database, including 663,160 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.85 (56336 hom., cov: 33)
  • Exomes 𝑓: 0.92 (606824 hom.)
• Consequence: BRDT NM_207189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.22

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.896804E-7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRDT	NM_207189.4	c.184C>A	p.Gln62Lys	missense_variant	2/19	ENST00000399546.7	NP_997072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRDT	ENST00000399546.7	c.184C>A	p.Gln62Lys	missense_variant	2/19	2	NM_207189.4	ENSP00000387822.3

Frequencies

GnomAD3 genomes AF: 0.853 AC: 129662 AN: 152074 Hom.: 56311 Cov.: 33

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.971

Gnomad AMR AF: 0.878

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.837

Gnomad FIN AF: 0.956

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.940

Gnomad OTH AF: 0.850

GnomAD3 exomes AF: 0.878 AC: 200165 AN: 227852 Hom.: 89196 AF XY: 0.884 AC XY: 109177 AN XY: 123506

Gnomad AFR exome AF: 0.692

Gnomad AMR exome AF: 0.885

Gnomad ASJ exome AF: 0.933

Gnomad EAS exome AF: 0.598

Gnomad SAS exome AF: 0.840

Gnomad FIN exome AF: 0.954

Gnomad NFE exome AF: 0.937

Gnomad OTH exome AF: 0.902

GnomAD4 exome AF: 0.917 AC: 1314533 AN: 1432882 Hom.: 606824 Cov.: 34 AF XY: 0.917 AC XY: 652669 AN XY: 712094

Gnomad4 AFR exome AF: 0.683

Gnomad4 AMR exome AF: 0.880

Gnomad4 ASJ exome AF: 0.931

Gnomad4 EAS exome AF: 0.591

Gnomad4 SAS exome AF: 0.845

Gnomad4 FIN exome AF: 0.954

Gnomad4 NFE exome AF: 0.941

Gnomad4 OTH exome AF: 0.897

GnomAD4 genome AF: 0.852 AC: 129732 AN: 152192 Hom.: 56336 Cov.: 33 AF XY: 0.854 AC XY: 63506 AN XY: 74402

Gnomad4 AFR AF: 0.697

Gnomad4 AMR AF: 0.879

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.837

Gnomad4 FIN AF: 0.956

Gnomad4 NFE AF: 0.940

Gnomad4 OTH AF: 0.843

Alfa AF: 0.915 Hom.: 166834

Bravo AF: 0.839

TwinsUK AF: 0.941 AC: 3489

ALSPAC AF: 0.945 AC: 3641

ESP6500AA AF: 0.699 AC: 3079

ESP6500EA AF: 0.941 AC: 8096

ExAC AF: 0.875 AC: 106288

Asia WGS AF: 0.729 AC: 2537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	9.7
DANN	Benign	0.83
DEOGEN2	Benign	0.048	T;.;.;.;.;.;.;T;.;.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.53	.;T;T;T;T;.;T;T;T;T;T
MetaRNN	Benign	5.9e-7	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.52	N;N;N;.;.;.;.;.;.;.;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.72	N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.036
Sift	Benign	0.58	T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.38	T;T;T;T;T;T;T;T;T;T;T
Polyphen		0.0	B;.;.;.;.;.;.;.;.;.;B
Vest4		0.037
MPC		0.10
ClinPred		0.0012	T
GERP RS		2.3
Varity_R		0.20
gMVP		0.30

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs10783071; hg19: chr1-92428495; COSMIC: COSV61771206; COSMIC: COSV61771206;