19-13889944-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001345843.2(BRME1):c.912G>A(p.Val304=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00151 in 1,612,688 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0014 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (3 hom.)
• Consequence: BRME1 NM_001345843.2 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.40

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-13889944-C-T is Benign according to our data. Variant chr19-13889944-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-2.4 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRME1	NM_001345843.2	c.912G>A	p.Val304=	synonymous_variant	6/9	ENST00000586783.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRME1	ENST00000586783.6	c.912G>A	p.Val304=	synonymous_variant	6/9	5	NM_001345843.2	P1
BRME1	ENST00000346736.6	c.912G>A	p.Val304=	synonymous_variant	6/8	2
BRME1	ENST00000591586.5	c.393+2842G>A		intron_variant		5
BRME1	ENST00000589393.1			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.00138 AC: 210 AN: 152202 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00621

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00198

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00156 AC: 388 AN: 248324 Hom.: 0 AF XY: 0.00162 AC XY: 218 AN XY: 134776

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.000200

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00694

Gnomad NFE exome AF: 0.00193

Gnomad OTH exome AF: 0.00181

GnomAD4 exome AF: 0.00152 AC: 2222 AN: 1460368 Hom.: 3 Cov.: 34 AF XY: 0.00158 AC XY: 1147 AN XY: 726550

Gnomad4 AFR exome AF: 0.000149

Gnomad4 AMR exome AF: 0.000179

Gnomad4 ASJ exome AF: 0.000230

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00725

Gnomad4 NFE exome AF: 0.00157

Gnomad4 OTH exome AF: 0.00104

GnomAD4 genome AF: 0.00138 AC: 210 AN: 152320 Hom.: 0 Cov.: 33 AF XY: 0.00142 AC XY: 106 AN XY: 74482

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00621

Gnomad4 NFE AF: 0.00198

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00135 Hom.: 0

Bravo AF: 0.000831

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2022

BRME1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	0.12
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs139071536; hg19: chr19-14000757;