11-66341562-T-C

Variant names:

• chr11-66341562-T-C
• rs11537993
• NM_015399.4:c.201A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4 BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 18 publications found

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]

ENSG00000254756 (HGNC:):

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015399.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRMS1	NM_015399.4	MANE Select	c.201A>G	p.Leu67Leu	synonymous	Exon 3 of 10	NP_056214.1	Q9HCU9
	BRMS1	NM_001024957.2		c.201A>G	p.Leu67Leu	synonymous	Exon 3 of 10	NP_001020128.1	G5E9I4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRMS1	ENST00000359957.8	TSL:1 MANE Select	c.201A>G	p.Leu67Leu	synonymous	Exon 3 of 10	ENSP00000353042.3	Q9HCU9
	BRMS1	ENST00000530756.1	TSL:1	c.201A>G	p.Leu67Leu	synonymous	Exon 3 of 9	ENSP00000433740.1	E9PJF5
	BRMS1	ENST00000877326.1		c.201A>G	p.Leu67Leu	synonymous	Exon 3 of 10	ENSP00000547385.1

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

GnomAD2 exomes AF: 0.246 AC: 61786 AN: 251328 AF XY: 0.255

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

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

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

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: 69 AN: 294

European-Non Finnish (NFE) AF: 0.331 AC: 22526 AN: 67970

Other (OTH) AF: 0.240 AC: 506 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	10
DANN	Benign	0.74
PhyloP100		2.0
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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