Variant 11-66340784-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015399.4(BRMS1):c.525C>T(p.Asp175Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00278 in 1,611,942 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 65 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 61 hom. )

Consequence

BRMS1
NM_015399.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.57

Variant links:

Genes affected

BRMS1 (HGNC:17262): (BRMS1 transcriptional repressor and anoikis regulator) This gene reduces the metastatic potential, but not the tumorogenicity, of human breast cancer and melanoma cell lines. The protein encoded by this gene localizes primarily to the nucleus and is a component of the mSin3a family of histone deacetylase complexes (HDAC). The protein contains two coiled-coil motifs and several imperfect leucine zipper motifs. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

BRMS1 links:

BRMS1 (HGNC:):

BRMS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP6

Variant 11-66340784-G-A is Benign according to our data. Variant chr11-66340784-G-A is described in ClinVar as [Benign]. Clinvar id is 776630.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=3.57 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRMS1	NM_015399.4 linkuse as main transcript	c.525C>T	p.Asp175Asp	synonymous_variant	6/10	ENST00000359957.8	NP_056214.1	Q9HCU9
BRMS1	NM_001024957.2 linkuse as main transcript	c.525C>T	p.Asp175Asp	synonymous_variant	6/10		NP_001020128.1	G5E9I4
BRMS1	XM_024448425.2 linkuse as main transcript	c.525C>T	p.Asp175Asp	synonymous_variant	6/9		XP_024304193.1
BRMS1	XM_024448426.2 linkuse as main transcript	c.525C>T	p.Asp175Asp	synonymous_variant	6/9		XP_024304194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRMS1	ENST00000359957.8 linkuse as main transcript	c.525C>T	p.Asp175Asp	synonymous_variant	6/10	1	NM_015399.4	ENSP00000353042.3		Q9HCU9

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2259

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0523

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00376

AC:

935

AN:

248638

Hom.:

AF XY:

0.00268

AC XY:

362

AN XY:

134826

show subpopulations

Gnomad AFR exome

AF:

0.0510

Gnomad AMR exome

AF:

0.00302

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000656

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000623

Gnomad OTH exome

AF:

0.00132

GnomAD4 exome

AF:

0.00152

AC:

2220

AN:

1459652

Hom.:

Cov.:

AF XY:

0.00127

AC XY:

924

AN XY:

726160

show subpopulations

Gnomad4 AFR exome

AF:

0.0554

Gnomad4 AMR exome

AF:

0.00304

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000163

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000333

Gnomad4 OTH exome

AF:

0.00289

GnomAD4 genome

AF:

0.0149

AC:

2264

AN:

152290

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

1098

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.0523

Gnomad4 AMR

AF:

0.00405

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00844

Hom.:

Bravo

AF:

0.0160

Asia WGS

AF:

0.00404

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 26, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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