Genetic Variant NM_015399.4:c.201A>G (chr11-66341562-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4BP7BA1

The NM_015399.4(BRMS1):c.201A>G(p.Leu67Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,672 control chromosomes in the GnomAD database, including 80,325 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 0.23 ( 5201 hom., cov: 32)

Exomes 𝑓: 0.31 ( 75124 hom. )

Consequence

BRMS1
NM_015399.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.04

Publications

18 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.243).

BP7

Synonymous conserved (PhyloP=2.04 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRMS1	NM_015399.4 link	c.201A>G	p.Leu67Leu	synonymous_variant	Exon 3 of 10	ENST00000359957.8	NP_056214.1	Q9HCU9
BRMS1	NM_001024957.2 link	c.201A>G	p.Leu67Leu	synonymous_variant	Exon 3 of 10		NP_001020128.1	G5E9I4
BRMS1	XM_024448425.2 link	c.201A>G	p.Leu67Leu	synonymous_variant	Exon 3 of 9		XP_024304193.1
BRMS1	XM_024448426.2 link	c.201A>G	p.Leu67Leu	synonymous_variant	Exon 3 of 9		XP_024304194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRMS1	ENST00000359957.8 link	c.201A>G	p.Leu67Leu	synonymous_variant	Exon 3 of 10	1	NM_015399.4	ENSP00000353042.3		Q9HCU9

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34971

AN:

152030

Hom.:

5204

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0680

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.371

Gnomad EAS

AF:

0.0306

Gnomad SAS

AF:

0.188

Gnomad FIN

AF:

0.345

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.243

GnomAD2 exomes

AF:

0.246

AC:

61786

AN:

251328

AF XY:

0.255

show subpopulations

Gnomad AFR exome

AF:

0.0606

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.376

Gnomad EAS exome

AF:

0.0306

Gnomad FIN exome

AF:

0.335

Gnomad NFE exome

AF:

0.325

Gnomad OTH exome

AF:

0.271

GnomAD4 exome

AF:

0.310

AC:

452574

AN:

1461524

Hom.:

75124

Cov.:

AF XY:

0.307

AC XY:

223387

AN XY:

727078

show subpopulations

African (AFR)

AF:

0.0568

AC:

1901

AN:

33480

American (AMR)

AF:

0.137

AC:

6110

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.377

AC:

9862

AN:

26136

East Asian (EAS)

AF:

0.0361

AC:

1433

AN:

39698

South Asian (SAS)

AF:

0.201

AC:

17355

AN:

86252

European-Finnish (FIN)

AF:

0.331

AC:

17641

AN:

53310

Middle Eastern (MID)

AF:

0.250

AC:

1442

AN:

5768

European-Non Finnish (NFE)

AF:

0.341

AC:

379322

AN:

1111776

Other (OTH)

AF:

0.290

AC:

17508

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

16965

33930

50896

67861

84826

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11966

23932

35898

47864

59830

<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:

0.230

AC:

34958

AN:

152148

Hom.:

5201

Cov.:

AF XY:

0.227

AC XY:

16873

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0678

AC:

2818

AN:

41540

American (AMR)

AF:

0.173

AC:

2641

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.371

AC:

1286

AN:

3470

East Asian (EAS)

AF:

0.0305

AC:

158

AN:

5180

South Asian (SAS)

AF:

0.187

AC:

900

AN:

4822

European-Finnish (FIN)

AF:

0.345

AC:

3646

AN:

10558

Middle Eastern (MID)

AF:

0.235

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22526

AN:

67970

Other (OTH)

AF:

0.240

AC:

506

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1303

2606

3908

5211

6514

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<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:

0.296

Hom.:

30910

Bravo

AF:

0.212

Asia WGS

AF:

0.102

AC:

358

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

2.0

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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