rs11537993

chr11-66341562-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_015399.4(BRMS1):c.201A>G(p.Leu67=) 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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• 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/exons	MANE	UniProt
BRMS1	NM_015399.4	c.201A>G	p.Leu67=	synonymous_variant	3/10	ENST00000359957.8
BRMS1	NM_001024957.2	c.201A>G	p.Leu67=	synonymous_variant	3/10
BRMS1	XM_024448425.2	c.201A>G	p.Leu67=	synonymous_variant	3/9
BRMS1	XM_024448426.2	c.201A>G	p.Leu67=	synonymous_variant	3/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRMS1	ENST00000359957.8	c.201A>G	p.Leu67=	synonymous_variant	3/10	1	NM_015399.4	P1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34971 AN: 152030 Hom.: 5204 Cov.: 32

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

GnomAD3 exomes AF: 0.246 AC: 61786 AN: 251328 Hom.: 9268 AF XY: 0.255 AC XY: 34595 AN XY: 135858

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 SAS exome AF: 0.197

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.: 41 AF XY: 0.307 AC XY: 223387 AN XY: 727078

Gnomad4 AFR exome AF: 0.0568

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.377

Gnomad4 EAS exome AF: 0.0361

Gnomad4 SAS exome AF: 0.201

Gnomad4 FIN exome AF: 0.331

Gnomad4 NFE exome AF: 0.341

Gnomad4 OTH exome AF: 0.290

GnomAD4 genome AF: 0.230 AC: 34958 AN: 152148 Hom.: 5201 Cov.: 32 AF XY: 0.227 AC XY: 16873 AN XY: 74364

Gnomad4 AFR AF: 0.0678

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.371

Gnomad4 EAS AF: 0.0305

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.345

Gnomad4 NFE AF: 0.331

Gnomad4 OTH AF: 0.240

Alfa AF: 0.304 Hom.: 16967

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	10
Dann	Benign	0.74

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

Other links and lift over

dbSNP: rs11537993; hg19: chr11-66109033; COSMIC: COSV60819970; COSMIC: COSV60819970;