Variant 19-13882951-G-A 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.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

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=0.01213333).

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 GnomAd at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BRME1	NM_001345843.2 linkuse as main transcript	c.1858C>T	p.Arg620Trp	missense_variant, splice_region_variant	9/9	ENST00000586783.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRME1	ENST00000586783.6 linkuse as main transcript	c.1858C>T	p.Arg620Trp	missense_variant, splice_region_variant	9/9	5	NM_001345843.2	P1	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

GnomAD3 exomes

AF:

0.00463

AC:

1146

AN:

247482

Hom.:

AF XY:

0.00502

AC XY:

673

AN XY:

134060

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 SAS exome

AF:

0.00563

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

Gnomad4 AFR exome

AF:

0.000990

Gnomad4 AMR exome

AF:

0.00235

Gnomad4 ASJ exome

AF:

0.00150

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00558

Gnomad4 FIN exome

AF:

0.000828

Gnomad4 NFE exome

AF:

0.00813

Gnomad4 OTH exome

AF:

0.00503

GnomAD4 genome

AF:

0.00431

AC:

655

AN:

152084

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00125

Gnomad4 AMR

AF:

0.00510

Gnomad4 ASJ

AF:

0.00202

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00584

Gnomad4 FIN

AF:

0.000754

Gnomad4 NFE

AF:

0.00696

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00665

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

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

Pathogenic

0.74

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Uncertain

0.040

Cadd

Uncertain

Dann

Pathogenic

1.0

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

MutationTaster

Benign

1.0

D;D;D;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

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

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