rs948360

Variant names:

• chr11-66339254-T-C
• rs948360
• NM_015399.4:c.629-469A>G

Variant summary

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

The NM_015399.4(BRMS1):​c.629-469A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.769 in 152,224 control chromosomes in the GnomAD database, including 49,077 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 0.77 (49077 hom., cov: 34)
• Consequence: BRMS1 NM_015399.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29
• Publications: 21 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 (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.922 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRMS1	NM_015399.4	c.629-469A>G		intron_variant	Intron 7 of 9	ENST00000359957.8	NP_056214.1
BRMS1	NM_001024957.2	c.629-469A>G		intron_variant	Intron 7 of 9		NP_001020128.1
BRMS1	XM_024448425.2	c.629-469A>G		intron_variant	Intron 7 of 8		XP_024304193.1
BRMS1	XM_024448426.2	c.629-469A>G		intron_variant	Intron 7 of 8		XP_024304194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRMS1	ENST00000359957.8	c.629-469A>G		intron_variant	Intron 7 of 9	1	NM_015399.4	ENSP00000353042.3

Frequencies

GnomAD3 genomes AF: 0.769 AC: 116963 AN: 152106 Hom.: 49075 Cov.: 34

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.957

Gnomad AMR AF: 0.869

Gnomad ASJ AF: 0.897

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.946

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.917

Gnomad OTH AF: 0.810

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.769 AC: 116990 AN: 152224 Hom.: 49077 Cov.: 34 AF XY: 0.776 AC XY: 57763 AN XY: 74424

African (AFR) AF: 0.395 AC: 16392 AN: 41482

American (AMR) AF: 0.869 AC: 13299 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.897 AC: 3114 AN: 3472

East Asian (EAS) AF: 0.830 AC: 4295 AN: 5172

South Asian (SAS) AF: 0.945 AC: 4565 AN: 4830

European-Finnish (FIN) AF: 0.953 AC: 10127 AN: 10628

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.917 AC: 62363 AN: 68028

Other (OTH) AF: 0.811 AC: 1712 AN: 2110

Alfa AF: 0.868 Hom.: 168599

Bravo AF: 0.744

Asia WGS AF: 0.859 AC: 2989 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.094
DANN	Benign	0.87
PhyloP100		-2.3
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: rs948360; hg19: chr11-66106725;