dbSNP rs77270337: BRME1:p.Arg620Trp (chr19-13882951-G-A) – 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.1858C>T(p.Arg620Trp) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00665 in 1,611,934 control chromosomes in the GnomAD database, including 55 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 53 hom. )

Consequence

BRME1
NM_001345843.2 missense, splice_region

Scores

Splicing: ADA: 0.9313

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.70

Publications

10 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=0.01213333).

BP6

Variant 19-13882951-G-A is Benign according to our data. Variant chr19-13882951-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2649402.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.1858C>T	p.Arg620Trp	missense_variant, splice_region_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.1858C>T	p.Arg620Trp	missense_variant, splice_region_variant	Exon 9 of 9	5	NM_001345843.2	ENSP00000465822.1		Q0VDD7-1

Frequencies

GnomAD3 genomes

AF:

0.00431

AC:

655

AN:

151966

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00511

Gnomad ASJ

AF:

0.00202

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00583

Gnomad FIN

AF:

0.000754

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00696

Gnomad OTH

AF:

0.00431

GnomAD2 exomes

AF:

0.00463

AC:

1146

AN:

247482

AF XY:

0.00502

show subpopulations

Gnomad AFR exome

AF:

0.000990

Gnomad AMR exome

AF:

0.00220

Gnomad ASJ exome

AF:

0.00140

Gnomad EAS exome

AF:

0.0000548

Gnomad FIN exome

AF:

0.000653

Gnomad NFE exome

AF:

0.00746

Gnomad OTH exome

AF:

0.00445

GnomAD4 exome

AF:

0.00689

AC:

10057

AN:

1459850

Hom.:

Cov.:

AF XY:

0.00692

AC XY:

5026

AN XY:

726310

show subpopulations

African (AFR)

AF:

0.000990

AC:

AN:

33332

American (AMR)

AF:

0.00235

AC:

104

AN:

44308

Ashkenazi Jewish (ASJ)

AF:

0.00150

AC:

AN:

26074

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00558

AC:

481

AN:

86178

European-Finnish (FIN)

AF:

0.000828

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00302

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

0.00813

AC:

9037

AN:

1111564

Other (OTH)

AF:

0.00503

AC:

303

AN:

60252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

536

1072

1608

2144

2680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00431

AC:

655

AN:

152084

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.00125

AC:

AN:

41468

American (AMR)

AF:

0.00510

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00202

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00584

AC:

AN:

4798

European-Finnish (FIN)

AF:

0.000754

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00696

AC:

473

AN:

67970

Other (OTH)

AF:

0.00426

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

130

163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00631

Hom.:

Bravo

AF:

0.00462

TwinsUK

AF:

0.00890

AC:

ALSPAC

AF:

0.00986

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00860

AC:

ExAC

AF:

0.00511

AC:

620

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00643

EpiControl

AF:

0.00741

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BRME1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.048

.;T;.;T

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.66

T;D;T;D

M_CAP

Benign

0.053

MetaRNN

Benign

0.0090

T;T;T;T

MetaSVM

Benign

-0.79

MutationAssessor

Benign

2.0

.;M;.;.

PhyloP100

5.7

PROVEAN

Pathogenic

-5.4

.;.;D;.

REVEL

Uncertain

0.38

Sift

Uncertain

0.0020

.;.;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.86, 0.80, 0.83

MVP

0.73

MPC

0.49

ClinPred

0.027

GERP RS

4.7

Varity_R

0.49

gMVP

0.070

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.93

dbscSNV1_RF

Benign

0.60

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

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rs77270337

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