11-66341562-T-A

Variant names:

• chr11-66341562-T-A
• rs11537993
• NM_015399.4:c.201A>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_015399.4(BRMS1):​c.201A>T​(p.Leu67Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: BRMS1 NM_015399.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.04
• Publications: 0 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP7: Synonymous conserved (PhyloP=2.04 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRMS1	NM_015399.4	c.201A>T	p.Leu67Leu	synonymous_variant	Exon 3 of 10	ENST00000359957.8	NP_056214.1
BRMS1	NM_001024957.2	c.201A>T	p.Leu67Leu	synonymous_variant	Exon 3 of 10		NP_001020128.1
BRMS1	XM_024448425.2	c.201A>T	p.Leu67Leu	synonymous_variant	Exon 3 of 9		XP_024304193.1
BRMS1	XM_024448426.2	c.201A>T	p.Leu67Leu	synonymous_variant	Exon 3 of 9		XP_024304194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRMS1	ENST00000359957.8	c.201A>T	p.Leu67Leu	synonymous_variant	Exon 3 of 10	1	NM_015399.4	ENSP00000353042.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	9.6
DANN	Benign	0.86
PhyloP100		2.0

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

Other links and lift over

dbSNP: rs11537993; hg19: chr11-66109033;