Variant 11-66340776-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015399.4(BRMS1):c.533C>T(p.Ser178Phe) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000109 in 1,611,232 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000098 ( 0 hom. )

Consequence

BRMS1
NM_015399.4 missense, splice_region

Scores

Splicing: ADA: 0.9566

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.41

Variant links:

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 links:

BRMS1 (HGNC:):

BRMS1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12906668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRMS1	NM_015399.4 linkuse as main transcript	c.533C>T	p.Ser178Phe	missense_variant, splice_region_variant	6/10	ENST00000359957.8	NP_056214.1	Q9HCU9
BRMS1	NM_001024957.2 linkuse as main transcript	c.533C>T	p.Ser178Phe	missense_variant, splice_region_variant	6/10		NP_001020128.1	G5E9I4
BRMS1	XM_024448425.2 linkuse as main transcript	c.533C>T	p.Ser178Phe	missense_variant, splice_region_variant	6/9		XP_024304193.1
BRMS1	XM_024448426.2 linkuse as main transcript	c.533C>T	p.Ser178Phe	missense_variant, splice_region_variant	6/9		XP_024304194.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRMS1	ENST00000359957.8 linkuse as main transcript	c.533C>T	p.Ser178Phe	missense_variant, splice_region_variant	6/10	1	NM_015399.4	ENSP00000353042.3		Q9HCU9

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000250

AC:

AN:

247960

Hom.:

AF XY:

0.000193

AC XY:

AN XY:

134478

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000697

Gnomad ASJ exome

AF:

0.00290

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000267

Gnomad OTH exome

AF:

0.000990

GnomAD4 exome

AF:

0.0000980

AC:

143

AN:

1459010

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

725794

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000627

Gnomad4 ASJ exome

AF:

0.00257

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.000266

GnomAD4 genome

AF:

0.000210

AC:

AN:

152222

Hom.:

Cov.:

AF XY:

0.000256

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00403

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000189

Hom.:

Bravo

AF:

0.000219

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000148

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 03, 2024

The c.533C>T (p.S178F) alteration is located in exon 6 (coding exon 5) of the BRMS1 gene. This alteration results from a C to T substitution at nucleotide position 533, causing the serine (S) at amino acid position 178 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Uncertain

0.058

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.20

T;T;.

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Uncertain

-0.22

MutationAssessor

Uncertain

2.1

.;M;.

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-4.0

D;D;D

REVEL

Uncertain

0.52

Sift

Uncertain

0.0010

D;D;D

Sift4G

Pathogenic

0.0010

D;D;.

Polyphen

0.96

D;P;.

Vest4

0.85

MVP

0.62

MPC

0.70

ClinPred

0.15

GERP RS

4.9

Varity_R

0.51

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.96

dbscSNV1_RF

Benign

0.52

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over