Genetic Variant BRME1:p.Arg638Gln (chr19-13882896-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001345843.2(BRME1):c.1913G>A(p.Arg638Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00646 in 1,613,752 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0067 ( 47 hom. )

Consequence

BRME1
NM_001345843.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.60

Publications

12 publications found

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 was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0051855147).

BP6

Variant 19-13882896-C-T is Benign according to our data. Variant chr19-13882896-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2649401.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRME1	NM_001345843.2 link	c.1913G>A	p.Arg638Gln	missense_variant	Exon 9 of 9	ENST00000586783.6	NP_001332772.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRME1	ENST00000586783.6 link	c.1913G>A	p.Arg638Gln	missense_variant	Exon 9 of 9	5	NM_001345843.2	ENSP00000465822.1		Q0VDD7-1

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

664

AN:

151880

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00545

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.00189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00722

Gnomad OTH

AF:

0.00337

GnomAD2 exomes

AF:

0.00428

AC:

1069

AN:

249620

AF XY:

0.00422

show subpopulations

Gnomad AFR exome

AF:

0.00123

Gnomad AMR exome

AF:

0.00371

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00314

Gnomad NFE exome

AF:

0.00721

Gnomad OTH exome

AF:

0.00376

GnomAD4 exome

AF:

0.00668

AC:

9761

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00645

AC XY:

4691

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.00161

AC:

AN:

33478

American (AMR)

AF:

0.00376

AC:

168

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.000153

AC:

AN:

26132

East Asian (EAS)

AF:

0.000176

AC:

AN:

39698

South Asian (SAS)

AF:

0.000997

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00333

AC:

178

AN:

53414

Middle Eastern (MID)

AF:

0.000349

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.00800

AC:

8896

AN:

1111962

Other (OTH)

AF:

0.00606

AC:

366

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

536

1072

1607

2143

2679

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00437

AC:

664

AN:

151998

Hom.:

Cov.:

AF XY:

0.00408

AC XY:

303

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.00128

AC:

AN:

41444

American (AMR)

AF:

0.00544

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00166

AC:

AN:

4814

European-Finnish (FIN)

AF:

0.00189

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00722

AC:

491

AN:

67964

Other (OTH)

AF:

0.00333

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

132

165

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00620

Hom.:

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00908

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00767

AC:

ExAC

AF:

0.00458

AC:

556

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00551

EpiControl

AF:

0.00646

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BRME1: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

.;T;.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.85

T;T;T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.0052

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

.;L;.;.

PhyloP100

1.6

PROVEAN

Uncertain

-2.8

.;.;D;.

REVEL

Benign

0.062

Sift

Pathogenic

0.0

.;.;D;.

Sift4G

Uncertain

0.050

T;D;D;T

Polyphen

0.75

.;P;P;.

Vest4

0.14, 0.23, 0.13

MVP

0.42

MPC

0.19

ClinPred

0.023

GERP RS

3.8

Varity_R

0.38

gMVP

0.021

Mutation Taster

=100/0

polymorphism

(source)

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

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19-13882896-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over