Genetic Variant BRINP1:p.Thr349Met (chr9-119208818-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014618.3(BRINP1):c.1046C>T(p.Thr349Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00207 in 1,614,190 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 15 hom. )

Consequence

BRINP1
NM_014618.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.16

Variant links:

Genes affected

BRINP1 (HGNC:2687): (BMP/retinoic acid inducible neural specific 1) This gene is located within a chromosomal region that shows loss of heterozygosity in some bladder cancers. It contains a 5' CpG island that may be a frequent target of hypermethylation, and it may undergo hypermethylation-based silencing in some bladder cancers. [provided by RefSeq, Jul 2008]

BRINP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0053915083).

BP6

Variant 9-119208818-G-A is Benign according to our data. Variant chr9-119208818-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 730457.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 268 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BRINP1	NM_014618.3 link	c.1046C>T	p.Thr349Met	missense_variant	Exon 7 of 8	ENST00000265922.8	NP_055433.2	O60477-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BRINP1	ENST00000265922.8 link	c.1046C>T	p.Thr349Met	missense_variant	Exon 7 of 8	1	NM_014618.3	ENSP00000265922.2		O60477-1
BRINP1	ENST00000482797.1 link	n.69C>T		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000265

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00190

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.00706

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00200

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00214

AC:

537

AN:

251278

Hom.:

AF XY:

0.00217

AC XY:

295

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00130

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00314

Gnomad FIN exome

AF:

0.00702

Gnomad NFE exome

AF:

0.00199

Gnomad OTH exome

AF:

0.00228

GnomAD4 exome

AF:

0.00210

AC:

3072

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00208

AC XY:

1515

AN XY:

727226

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00321

Gnomad4 FIN exome

AF:

0.00582

Gnomad4 NFE exome

AF:

0.00207

Gnomad4 OTH exome

AF:

0.00189

GnomAD4 genome

AF:

0.00176

AC:

268

AN:

152328

Hom.:

Cov.:

AF XY:

0.00199

AC XY:

148

AN XY:

74480

show subpopulations

Gnomad4 AFR

AF:

0.000265

Gnomad4 AMR

AF:

0.00190

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00706

Gnomad4 NFE

AF:

0.00200

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00174

Hom.:

Bravo

AF:

0.00136

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00256

AC:

ExAC

AF:

0.00208

AC:

252

Asia WGS

AF:

0.00202

AC:

AN:

3476

EpiCase

AF:

0.00196

EpiControl

AF:

0.00160

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.65

CADD

Benign

2.2

DANN

Benign

0.18

DEOGEN2

Benign

0.020

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.96

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.66

M_CAP

Benign

0.0030

MetaRNN

Benign

0.0054

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.58

PrimateAI

Benign

0.31

PROVEAN

Benign

0.51

REVEL

Benign

0.017

Sift

Benign

1.0

Sift4G

Benign

0.35

Polyphen

0.0030

Vest4

0.16

MVP

0.093

MPC

0.46

ClinPred

0.0011

GERP RS

-0.89

Varity_R

0.016

gMVP

0.29

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

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