dbSNP rs1052566: BRMS1:c.*159C>T (chr11-66337723-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001024957.2(BRMS1):c.818C>T(p.Ala273Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,609,178 control chromosomes in the GnomAD database, including 75,872 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5383 hom., cov: 32)

Exomes 𝑓: 0.30 ( 70489 hom. )

Consequence

BRMS1
NM_001024957.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

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:

ENSG00000254756 (HGNC:):

ENSG00000254756 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.472174E-5).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.51 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRMS1	NM_015399.4 link	c.*159C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000359957.8	NP_056214.1	Q9HCU9
BRMS1	NM_001024957.2 link	c.818C>T	p.Ala273Val	missense_variant	Exon 10 of 10		NP_001020128.1	G5E9I4
BRMS1	XM_024448425.2 link	c.860C>T	p.Ala287Val	missense_variant	Exon 9 of 9		XP_024304193.1
BRMS1	XM_024448426.2 link	c.778C>T	p.Pro260Ser	missense_variant	Exon 9 of 9		XP_024304194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRMS1	ENST00000359957 link	c.*159C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_015399.4	ENSP00000353042.3		Q9HCU9

Frequencies

GnomAD3 genomes

AF:

0.241

AC:

36576

AN:

151970

Hom.:

5381

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0744

Gnomad AMI

AF:

0.405

Gnomad AMR

AF:

0.286

Gnomad ASJ

AF:

0.254

Gnomad EAS

AF:

0.338

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.231

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.250

GnomAD3 exomes

AF:

0.301

AC:

72565

AN:

241382

Hom.:

12300

AF XY:

0.315

AC XY:

41222

AN XY:

131038

show subpopulations

Gnomad AFR exome

AF:

0.0738

Gnomad AMR exome

AF:

0.252

Gnomad ASJ exome

AF:

0.239

Gnomad EAS exome

AF:

0.319

Gnomad SAS exome

AF:

0.526

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.299

Gnomad OTH exome

AF:

0.309

GnomAD4 exome

AF:

0.303

AC:

441553

AN:

1457090

Hom.:

70489

Cov.:

AF XY:

0.310

AC XY:

224745

AN XY:

724626

show subpopulations

Gnomad4 AFR exome

AF:

0.0637

Gnomad4 AMR exome

AF:

0.253

Gnomad4 ASJ exome

AF:

0.245

Gnomad4 EAS exome

AF:

0.361

Gnomad4 SAS exome

AF:

0.520

Gnomad4 FIN exome

AF:

0.244

Gnomad4 NFE exome

AF:

0.298

Gnomad4 OTH exome

AF:

0.300

GnomAD4 genome

AF:

0.241

AC:

36581

AN:

152088

Hom.:

5383

Cov.:

AF XY:

0.244

AC XY:

18149

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0741

Gnomad4 AMR

AF:

0.286

Gnomad4 ASJ

AF:

0.254

Gnomad4 EAS

AF:

0.338

Gnomad4 SAS

AF:

0.527

Gnomad4 FIN

AF:

0.231

Gnomad4 NFE

AF:

0.302

Gnomad4 OTH

AF:

0.254

Alfa

AF:

0.279

Hom.:

6572

Bravo

AF:

0.228

TwinsUK

AF:

0.280

AC:

1038

ALSPAC

AF:

0.298

AC:

1149

ESP6500AA

AF:

0.0810

AC:

356

ESP6500EA

AF:

0.298

AC:

2563

ExAC

AF:

0.299

AC:

36277

Asia WGS

AF:

0.396

AC:

1375

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.26

DANN

Benign

0.77

DEOGEN2

Benign

0.016

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.28

MetaRNN

Benign

0.000065

MetaSVM

Benign

-0.93

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.21

REVEL

Benign

0.10

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.024

MPC

0.17

ClinPred

0.00030

GERP RS

-4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.085

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over