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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015399.4(BRMS1):c.*159C>T variant causes a 3 prime UTR 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. 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_015399.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

28 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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
BRMS1	NM_015399.4 link	c.*159C>T		3_prime_UTR_variant	Exon 10 of 10	ENST00000359957.8	NP_056214.1
BRMS1	NM_001024957.2 link	c.818C>T	p.Ala273Val	missense_variant	Exon 10 of 10		NP_001020128.1
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	ENST00000359957.8 link	c.*159C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_015399.4	ENSP00000353042.3

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

GnomAD2 exomes

AF:

0.301

AC:

72565

AN:

241382

AF XY:

0.315

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 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

African (AFR)

AF:

0.0637

AC:

2128

AN:

33410

American (AMR)

AF:

0.253

AC:

11087

AN:

43904

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

6398

AN:

26082

East Asian (EAS)

AF:

0.361

AC:

14296

AN:

39598

South Asian (SAS)

AF:

0.520

AC:

44692

AN:

85896

European-Finnish (FIN)

AF:

0.244

AC:

12922

AN:

52860

Middle Eastern (MID)

AF:

0.330

AC:

1664

AN:

5038

European-Non Finnish (NFE)

AF:

0.298

AC:

330347

AN:

1110172

Other (OTH)

AF:

0.300

AC:

18019

AN:

60130

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

17456

34912

52369

69825

87281

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10856

21712

32568

43424

54280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.241

AC:

36581

AN:

152088

Hom.:

5383

Cov.:

AF XY:

0.244

AC XY:

18149

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.0741

AC:

3077

AN:

41536

American (AMR)

AF:

0.286

AC:

4380

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.254

AC:

881

AN:

3470

East Asian (EAS)

AF:

0.338

AC:

1740

AN:

5146

South Asian (SAS)

AF:

0.527

AC:

2535

AN:

4812

European-Finnish (FIN)

AF:

0.231

AC:

2451

AN:

10592

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.302

AC:

20516

AN:

67928

Other (OTH)

AF:

0.254

AC:

537

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1360

2721

4081

5442

6802

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

394

788

1182

1576

1970

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.271

Hom.:

9307

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

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

0.26

(source)

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

PhyloP100

-1.5

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

Mutation Taster

=100/0

polymorphism (auto)

(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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over