rs1052566

chr11-66337723-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
BRMS1	NM_015399.4	c.*159C>T		3_prime_UTR_variant	10/10	ENST00000359957.8
BRMS1	NM_001024957.2	c.818C>T	p.Ala273Val	missense_variant	10/10
BRMS1	XM_024448425.2	c.860C>T	p.Ala287Val	missense_variant	9/9
BRMS1	XM_024448426.2	c.778C>T	p.Pro260Ser	missense_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRMS1	ENST00000359957.8	c.*159C>T		3_prime_UTR_variant	10/10	1	NM_015399.4	P1
	ENST00000526655.1	n.423+1258G>A		intron_variant, non_coding_transcript_variant		3

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

GnomAD3 exomes AF: 0.301 AC: 72565 AN: 241382 Hom.: 12300 AF XY: 0.315 AC XY: 41222 AN XY: 131038

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 SAS exome AF: 0.526

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

Gnomad4 AFR exome AF: 0.0637

Gnomad4 AMR exome AF: 0.253

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.361

Gnomad4 SAS exome AF: 0.520

Gnomad4 FIN exome AF: 0.244

Gnomad4 NFE exome AF: 0.298

Gnomad4 OTH exome AF: 0.300

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

Gnomad4 AFR AF: 0.0741

Gnomad4 AMR AF: 0.286

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.338

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.302

Gnomad4 OTH AF: 0.254

Alfa AF: 0.279 Hom.: 6572

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
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
MutationTaster	Benign	1.0	P;P
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

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