rs3116068

Positions:

• chr11-66337522-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015399.4(BRMS1):​c.*360G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 691,074 control chromosomes in the GnomAD database, including 13,951 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 0.17 (2570 hom., cov: 33)
  • Exomes 𝑓: 0.20 (11381 hom.)
• Consequence: BRMS1 NM_015399.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRMS1	NM_015399.4	c.*360G>A		3_prime_UTR_variant	10/10	ENST00000359957.8	NP_056214.1
BRMS1	NM_001024957.2	c.*146G>A		3_prime_UTR_variant	10/10		NP_001020128.1
BRMS1	XM_024448425.2	c.*146G>A		3_prime_UTR_variant	9/9		XP_024304193.1
BRMS1	XM_024448426.2	c.*112G>A		3_prime_UTR_variant	9/9		XP_024304194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRMS1	ENST00000359957.8	c.*360G>A		3_prime_UTR_variant	10/10	1	NM_015399.4	ENSP00000353042.3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25940 AN: 152104 Hom.: 2572 Cov.: 33

Gnomad AFR AF: 0.0829

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.249

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.200

GnomAD4 exome AF: 0.201 AC: 108244 AN: 538852 Hom.: 11381 Cov.: 7 AF XY: 0.199 AC XY: 55414 AN XY: 278144

Gnomad4 AFR exome AF: 0.0860

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.241

Gnomad4 EAS exome AF: 0.247

Gnomad4 SAS exome AF: 0.136

Gnomad4 FIN exome AF: 0.245

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.170 AC: 25933 AN: 152222 Hom.: 2570 Cov.: 33 AF XY: 0.174 AC XY: 12961 AN XY: 74414

Gnomad4 AFR AF: 0.0827

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.141

Gnomad4 FIN AF: 0.249

Gnomad4 NFE AF: 0.207

Gnomad4 OTH AF: 0.202

Alfa AF: 0.202 Hom.: 622

Bravo AF: 0.162

Asia WGS AF: 0.198 AC: 690 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.48
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3116068; hg19: chr11-66104993; COSMIC: COSV60927021; COSMIC: COSV60927021;