rs948360

chr11-66339254-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 (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/exons	MANE	UniProt
BRMS1	NM_015399.4	c.629-469A>G		intron_variant		ENST00000359957.8
BRMS1	NM_001024957.2	c.629-469A>G		intron_variant
BRMS1	XM_024448425.2	c.629-469A>G		intron_variant
BRMS1	XM_024448426.2	c.629-469A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BRMS1	ENST00000359957.8	c.629-469A>G		intron_variant		1	NM_015399.4	P1
	ENST00000526655.1	n.424-529T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.395

Gnomad4 AMR AF: 0.869

Gnomad4 ASJ AF: 0.897

Gnomad4 EAS AF: 0.830

Gnomad4 SAS AF: 0.945

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.917

Gnomad4 OTH AF: 0.811

Alfa AF: 0.890 Hom.: 82635

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

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: rs948360; hg19: chr11-66106725;