11-66337723-G-A

Variant names:

• chr11-66337723-G-A
• rs1052566
• NM_015399.4:c.*159C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.46
• Publications: 28 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 -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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRMS1	NM_015399.4	MANE Select	c.*159C>T		3_prime_UTR	Exon 10 of 10	NP_056214.1
	BRMS1	NM_001024957.2		c.818C>T	p.Ala273Val	missense	Exon 10 of 10	NP_001020128.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRMS1	ENST00000359957.8	TSL:1 MANE Select	c.*159C>T		3_prime_UTR	Exon 10 of 10	ENSP00000353042.3
	BRMS1	ENST00000425825.6	TSL:5	c.818C>T	p.Ala273Val	missense	Exon 10 of 10	ENSP00000396052.2
	BRMS1	ENST00000524699.5	TSL:3	c.746C>T	p.Ala249Val	missense	Exon 8 of 8	ENSP00000431510.1

Frequencies

GnomAD3 genomes AF: 0.241 AC: 36576 AN: 151970 Hom.: 5381 Cov.: 32

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

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.: 38 AF XY: 0.310 AC XY: 224745 AN XY: 724626

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

GnomAD4 genome AF: 0.241 AC: 36581 AN: 152088 Hom.: 5383 Cov.: 32 AF XY: 0.244 AC XY: 18149 AN XY: 74326

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: 95 AN: 294

European-Non Finnish (NFE) AF: 0.302 AC: 20516 AN: 67928

Other (OTH) AF: 0.254 AC: 537 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.26
DANN	Benign	0.77
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.000065	T
MetaSVM	Benign	-0.93	T
PhyloP100		-1.5
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.10
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.024
MPC		0.17
ClinPred		0.00030	T
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)

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: rs1052566; hg19: chr11-66105194; COSMIC: COSV60925600; COSMIC: COSV60925600;