Variant 19-13889383-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001345843.2(BRME1):c.1473C>A(p.Asp491Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00816 in 1,614,088 control chromosomes in the GnomAD database, including 78 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0056 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0084 ( 74 hom. )

Consequence

BRME1
NM_001345843.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.866

Variant links:

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]

BRME1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0048757493).

BP6

Variant 19-13889383-G-T is Benign according to our data. Variant chr19-13889383-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649403.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRME1	NM_001345843.2 linkuse as main transcript	c.1473C>A	p.Asp491Glu	missense_variant	6/9	ENST00000586783.6	NP_001332772.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRME1	ENST00000586783.6 linkuse as main transcript	c.1473C>A	p.Asp491Glu	missense_variant	6/9	5	NM_001345843.2	ENSP00000465822	P1	Q0VDD7-1

Frequencies

GnomAD3 genomes

AF:

0.00562

AC:

856

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00181

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00352

Gnomad FIN

AF:

0.00339

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00976

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00526

AC:

1321

AN:

251298

Hom.:

AF XY:

0.00565

AC XY:

768

AN XY:

135810

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00208

Gnomad ASJ exome

AF:

0.00109

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00274

Gnomad FIN exome

AF:

0.00347

Gnomad NFE exome

AF:

0.00916

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00843

AC:

12316

AN:

1461784

Hom.:

Cov.:

AF XY:

0.00840

AC XY:

6105

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.00116

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00107

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00334

Gnomad4 FIN exome

AF:

0.00328

Gnomad4 NFE exome

AF:

0.0102

Gnomad4 OTH exome

AF:

0.00573

GnomAD4 genome

AF:

0.00562

AC:

856

AN:

152304

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

405

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00180

Gnomad4 AMR

AF:

0.00177

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00352

Gnomad4 FIN

AF:

0.00339

Gnomad4 NFE

AF:

0.00976

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00830

Hom.:

Bravo

AF:

0.00510

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.0122

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00988

AC:

ExAC

AF:

0.00523

AC:

635

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00823

EpiControl

AF:

0.00830

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

BRME1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.5

DANN

Benign

0.90

DEOGEN2

Benign

0.0026

T;.;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.062

LIST_S2

Benign

0.30

T;T;T

M_CAP

Benign

0.0077

MetaRNN

Benign

0.0049

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;.

MutationTaster

Benign

1.0

N;N;N;N

PROVEAN

Benign

-1.6

.;N;.

REVEL

Benign

0.034

Sift

Benign

0.049

.;D;.

Sift4G

Benign

0.16

T;T;T

Polyphen

0.013

B;B;.

Vest4

0.036

MutPred

0.16

Gain of solvent accessibility (P = 0.0638);Gain of solvent accessibility (P = 0.0638);.;

MVP

0.38

MPC

0.085

ClinPred

0.0064

GERP RS

1.3

Varity_R

0.060

gMVP

0.018

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over