1-91949492-G-C

Position:

• chr1-91949492-G-C

Variant summary

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

The NM_001242807.2(BRDT):​c.-38+4G>C variant causes a splice region, intron 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. 3/3 splice prediction tools predict no significant impact on normal splicing. 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_001242807.2 splice_region, intron
• Scores: Splicing: ADA: 0.00002108
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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 (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/exons	MANE	Protein	UniProt
BRDT	NM_207189.4	c.-228G>C		5_prime_UTR_variant	1/19	ENST00000399546.7	NP_997072.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRDT	ENST00000399546	c.-228G>C		5_prime_UTR_variant	1/19	2	NM_207189.4	ENSP00000387822.3

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44443 AN: 152004 Hom.: 7682 Cov.: 33

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: 6 AN: 20 Hom.: 1 Cov.: 0 AF XY: 0.278 AC XY: 5 AN XY: 18

Gnomad4 NFE exome AF: 0.278

GnomAD4 genome AF: 0.293 AC: 44524 AN: 152122 Hom.: 7718 Cov.: 33 AF XY: 0.288 AC XY: 21423 AN XY: 74372

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.403

Gnomad4 SAS AF: 0.235

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.297

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
DANN	Benign	0.44

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

LitVar

Other links and lift over

dbSNP: rs11165878; hg19: chr1-92415049;