rs3088232

Positions:

• chr1-91979700-C-G
• chr1-91979700-C-T

Variant summary

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

The NM_207189.4(BRDT):​c.1230C>G​(p.Asn410Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 1,612,400 control chromosomes in the GnomAD database, including 46,807 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.18 (3133 hom., cov: 32)
  • Exomes 𝑓: 0.24 (43674 hom.)
• Consequence: BRDT NM_207189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

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=0.0022077262).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRDT	NM_207189.4	c.1230C>G	p.Asn410Lys	missense_variant	8/19	ENST00000399546.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRDT	ENST00000399546.7	c.1230C>G	p.Asn410Lys	missense_variant	8/19	2	NM_207189.4	P1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27430 AN: 152018 Hom.: 3122 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.189

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0320

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.188

GnomAD3 exomes AF: 0.212 AC: 52982 AN: 250326 Hom.: 6402 AF XY: 0.216 AC XY: 29189 AN XY: 135340

Gnomad AFR exome AF: 0.0472

Gnomad AMR exome AF: 0.224

Gnomad ASJ exome AF: 0.253

Gnomad EAS exome AF: 0.0220

Gnomad SAS exome AF: 0.213

Gnomad FIN exome AF: 0.255

Gnomad NFE exome AF: 0.250

Gnomad OTH exome AF: 0.215

GnomAD4 exome AF: 0.238 AC: 347928 AN: 1460264 Hom.: 43674 Cov.: 33 AF XY: 0.238 AC XY: 173238 AN XY: 726406

Gnomad4 AFR exome AF: 0.0463

Gnomad4 AMR exome AF: 0.220

Gnomad4 ASJ exome AF: 0.247

Gnomad4 EAS exome AF: 0.0434

Gnomad4 SAS exome AF: 0.215

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.254

Gnomad4 OTH exome AF: 0.223

GnomAD4 genome AF: 0.181 AC: 27462 AN: 152136 Hom.: 3133 Cov.: 32 AF XY: 0.179 AC XY: 13344 AN XY: 74346

Gnomad4 AFR AF: 0.0539

Gnomad4 AMR AF: 0.190

Gnomad4 ASJ AF: 0.252

Gnomad4 EAS AF: 0.0319

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.247

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.186

Alfa AF: 0.217 Hom.: 2479

Bravo AF: 0.170

TwinsUK AF: 0.261 AC: 968

ALSPAC AF: 0.257 AC: 989

ESP6500AA AF: 0.0590 AC: 260

ESP6500EA AF: 0.248 AC: 2137

ExAC AF: 0.211 AC: 25631

Asia WGS AF: 0.115 AC: 399 AN: 3478

EpiCase AF: 0.244

EpiControl AF: 0.246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	4.4
DANN	Uncertain	0.98
DEOGEN2	Benign	0.063	T;.;.;.;T;T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.26	N
MetaRNN	Benign	0.0022	T;T;T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.1	L;.;.;.;.;L
MutationTaster	Benign	0.92	P;P;P;P;P
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.4	N;N;N;.;N;N
REVEL	Benign	0.040
Sift	Benign	0.28	T;T;T;.;T;T
Sift4G	Benign	0.55	T;T;T;T;T;T
Polyphen		0.0030	B;.;.;.;.;B
Vest4		0.056
MutPred		0.27		Gain of ubiquitination at N410 (P = 0.0054);.;.;.;Gain of ubiquitination at N410 (P = 0.0054);Gain of ubiquitination at N410 (P = 0.0054);
MPC		0.091
ClinPred		0.0037	T
GERP RS		3.8
Varity_R		0.12
gMVP		0.070

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: rs3088232; hg19: chr1-92445257; COSMIC: COSV62864533; COSMIC: COSV62864533;