rs3745457

Positions:

• chr19-13905961-G-A
• chr19-13905961-G-T

Variant summary

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

The NM_001345843.2(BRME1):​c.-268C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 149,260 control chromosomes in the GnomAD database, including 8,040 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (8030 hom., cov: 30)
  • Exomes 𝑓: 0.32 (10 hom.)
• Consequence: BRME1 NM_001345843.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

Genes affected

BRME1 (HGNC:28153): (break repair meiotic recombinase recruitment factor 1) Predicted to be involved in meiosis I and spermatogenesis. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRME1	NM_001345843.2	c.-268C>T		5_prime_UTR_variant	1/9	ENST00000586783.6	NP_001332772.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRME1	ENST00000586783.6	c.-268C>T		5_prime_UTR_variant	1/9	5	NM_001345843.2	ENSP00000465822	P1
BRME1	ENST00000591586.5	c.-268C>T		5_prime_UTR_variant	1/8	5		ENSP00000466723
BRME1	ENST00000346736.6	c.-22+98C>T		intron_variant		2		ENSP00000254336
BRME1	ENST00000585755.1	c.-22+228C>T		intron_variant		3		ENSP00000466119

Frequencies

GnomAD3 genomes AF: 0.307 AC: 45680 AN: 148952 Hom.: 8001 Cov.: 30

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.247

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.288

Gnomad FIN AF: 0.165

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.325 AC: 63 AN: 194 Hom.: 10 Cov.: 0 AF XY: 0.268 AC XY: 30 AN XY: 112

Gnomad4 AFR exome AF: 0.563

Gnomad4 AMR exome AF: 0.750

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.167

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.438

GnomAD4 genome AF: 0.307 AC: 45757 AN: 149066 Hom.: 8030 Cov.: 30 AF XY: 0.302 AC XY: 22001 AN XY: 72888

Gnomad4 AFR AF: 0.546

Gnomad4 AMR AF: 0.247

Gnomad4 ASJ AF: 0.142

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.287

Gnomad4 FIN AF: 0.165

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.273

Alfa AF: 0.279 Hom.: 714

Asia WGS AF: 0.351 AC: 1219 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.83

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3745457; hg19: chr19-14016774;