rs11165878

Variant names:

• chr1-91949492-G-C
• rs11165878
• NM_207189.4:c.-228G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-91949492-G-C
• chr1-91949492-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001242807.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRDT	NM_207189.4	MANE Select	c.-228G>C		5_prime_UTR	Exon 1 of 19	NP_997072.2
	BRDT	NM_001242806.2		c.-228G>C		5_prime_UTR	Exon 1 of 19	NP_001229735.2
	BRDT	NM_001242805.2		c.-297G>C		5_prime_UTR	Exon 1 of 20	NP_001229734.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRDT	ENST00000399546.7	TSL:2 MANE Select	c.-228G>C		5_prime_UTR	Exon 1 of 19	ENSP00000387822.3
	BRDT	ENST00000362005.7	TSL:1	c.-297G>C		5_prime_UTR	Exon 1 of 20	ENSP00000354568.3
	BRDT	ENST00000370389.6	TSL:1	c.-803G>C		5_prime_UTR	Exon 1 of 19	ENSP00000359416.2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.278 AC: 5 AN: 18

Other (OTH) AC: 0 AN: 0

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

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: 49 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14330 AN: 68000

Other (OTH) AF: 0.297 AC: 627 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		-1.6
PromoterAI		0.028	Neutral
Mutation Taster		=298/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11165878; hg19: chr1-92415049;