Genetic Variant BRI3:p.Glu9Gly (chr7-98281821-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015379.5(BRI3):c.26A>G(p.Glu9Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000605 in 1,255,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000063 ( 0 hom. )

Consequence

BRI3
NM_015379.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.938

Publications

0 publications found

Variant links:

Genes affected

BRI3 (HGNC:1109): (brain protein I3) Enables identical protein binding activity. Predicted to be located in azurophil granule membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

BRI3 links:

ENSG00000296691 (HGNC:):

ENSG00000296691 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10367012).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015379.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BRI3	NM_015379.5	MANE Select	c.26A>G	p.Glu9Gly	missense	Exon 1 of 3	NP_056194.1	O95415-1
	BRI3	NM_001159491.2		c.26A>G	p.Glu9Gly	missense	Exon 1 of 3	NP_001152963.1	O95415-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
BRI3	ENST00000297290.4	TSL:1 MANE Select	c.26A>G	p.Glu9Gly	missense	Exon 1 of 3	ENSP00000297290.3	O95415-1
BRI3	ENST00000539286.5	TSL:2	c.26A>G	p.Glu9Gly	missense	Exon 1 of 3	ENSP00000440936.1	O95415-2
BRI3	ENST00000456357.6	TSL:2	n.151-530A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000404

AC:

AN:

148578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00105

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000492

GnomAD2 exomes

AF:

0.000138

AC:

AN:

7226

AF XY:

0.000228

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000632

AC:

AN:

1106728

Hom.:

Cov.:

AF XY:

0.0000888

AC XY:

AN XY:

529294

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

22772

American (AMR)

AF:

0.00

AC:

AN:

9522

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14676

East Asian (EAS)

AF:

0.00

AC:

AN:

25794

South Asian (SAS)

AF:

0.00121

AC:

AN:

32962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23172

Middle Eastern (MID)

AF:

0.00135

AC:

AN:

2972

European-Non Finnish (NFE)

AF:

0.0000193

AC:

AN:

930826

Other (OTH)

AF:

0.000182

AC:

AN:

44032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000404

AC:

AN:

148680

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

72654

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40240

American (AMR)

AF:

0.00

AC:

AN:

15062

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3438

East Asian (EAS)

AF:

0.00

AC:

AN:

4966

South Asian (SAS)

AF:

0.00105

AC:

AN:

4748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9966

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67016

Other (OTH)

AF:

0.000486

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.000378

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.59

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.031

Eigen

Benign

-0.043

Eigen_PC

Benign

-0.028

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.66

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.10

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

PhyloP100

0.94

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-2.1

REVEL

Benign

0.13

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.020

Polyphen

0.97

Vest4

0.13

MutPred

0.14

Loss of solvent accessibility (P = 0.0387)

MVP

0.32

MPC

0.42

ClinPred

0.22

GERP RS

3.9

PromoterAI

-0.019

Neutral

(source)

Varity_R

0.22

gMVP

0.65

Mutation Taster

=67/33

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over