1-91992286-C-T

Variant names:

• chr1-91992286-C-T
• rs10747493
• NM_207189.4:c.2087C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_207189.4(BRDT):​c.2087C>T​(p.Pro696Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.834 in 1,501,474 control chromosomes in the GnomAD database, including 526,259 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.78 (47177 hom., cov: 30)
  • Exomes 𝑓: 0.84 (479082 hom.)
• Consequence: BRDT NM_207189.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926
• Publications: 27 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.419746E-6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207189.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRDT	NM_207189.4	MANE Select	c.2087C>T	p.Pro696Leu	missense	Exon 14 of 19	NP_997072.2
	BRDT	NM_001242806.2		c.2099C>T	p.Pro700Leu	missense	Exon 14 of 19	NP_001229735.2
	BRDT	NM_001242805.2		c.2087C>T	p.Pro696Leu	missense	Exon 15 of 20	NP_001229734.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRDT	ENST00000399546.7	TSL:2 MANE Select	c.2087C>T	p.Pro696Leu	missense	Exon 14 of 19	ENSP00000387822.3
	BRDT	ENST00000362005.7	TSL:1	c.2087C>T	p.Pro696Leu	missense	Exon 15 of 20	ENSP00000354568.3
	BRDT	ENST00000402388.1	TSL:1	c.2087C>T	p.Pro696Leu	missense	Exon 14 of 19	ENSP00000384051.1

Frequencies

GnomAD3 genomes AF: 0.783 AC: 118502 AN: 151434 Hom.: 47155 Cov.: 30

Gnomad AFR AF: 0.627

Gnomad AMI AF: 0.929

Gnomad AMR AF: 0.813

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.814

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.839

Gnomad NFE AF: 0.855

Gnomad OTH AF: 0.774

GnomAD2 exomes AF: 0.814 AC: 158832 AN: 195216 AF XY: 0.820

Gnomad AFR exome AF: 0.609

Gnomad AMR exome AF: 0.825

Gnomad ASJ exome AF: 0.881

Gnomad EAS exome AF: 0.581

Gnomad FIN exome AF: 0.904

Gnomad NFE exome AF: 0.847

Gnomad OTH exome AF: 0.823

GnomAD4 exome AF: 0.840 AC: 1133720 AN: 1349926 Hom.: 479082 Cov.: 27 AF XY: 0.840 AC XY: 564356 AN XY: 671722

African (AFR) AF: 0.601 AC: 17133 AN: 28492

American (AMR) AF: 0.822 AC: 23993 AN: 29186

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 21165 AN: 24010

East Asian (EAS) AF: 0.582 AC: 21041 AN: 36130

South Asian (SAS) AF: 0.816 AC: 56743 AN: 69560

European-Finnish (FIN) AF: 0.899 AC: 47191 AN: 52488

Middle Eastern (MID) AF: 0.827 AC: 4544 AN: 5492

European-Non Finnish (NFE) AF: 0.854 AC: 895503 AN: 1048402

Other (OTH) AF: 0.826 AC: 46407 AN: 56166

GnomAD4 genome AF: 0.782 AC: 118561 AN: 151548 Hom.: 47177 Cov.: 30 AF XY: 0.787 AC XY: 58298 AN XY: 74078

African (AFR) AF: 0.627 AC: 25879 AN: 41306

American (AMR) AF: 0.814 AC: 12392 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3110 AN: 3468

East Asian (EAS) AF: 0.598 AC: 3065 AN: 5128

South Asian (SAS) AF: 0.813 AC: 3906 AN: 4804

European-Finnish (FIN) AF: 0.907 AC: 9421 AN: 10384

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.855 AC: 58076 AN: 67916

Other (OTH) AF: 0.769 AC: 1619 AN: 2106

Alfa AF: 0.826 Hom.: 232133

Bravo AF: 0.766

TwinsUK AF: 0.866 AC: 3210

ALSPAC AF: 0.857 AC: 3304

ESP6500AA AF: 0.628 AC: 2765

ESP6500EA AF: 0.855 AC: 7347

ExAC AF: 0.811 AC: 98434

Asia WGS AF: 0.708 AC: 2449 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.22
DANN	Benign	0.15
DEOGEN2	Benign	0.058	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.25	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-0.81	N
PhyloP100		-0.93
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.0030
Sift	Benign	1.0	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.047
MPC		0.081
ClinPred		0.0016	T
GERP RS		0.031
Varity_R		0.020
gMVP		0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10747493; hg19: chr1-92457843; COSMIC: COSV104539070;