dbSNP rs1261113270: BRI3:p.Pro5Ala (chr7-98281808-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015379.5(BRI3):c.13C>G(p.Pro5Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000134 in 149,316 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Consequence

BRI3
NM_015379.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25687045).

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.13C>G	p.Pro5Ala	missense	Exon 1 of 3	NP_056194.1	O95415-1
	BRI3	NM_001159491.2		c.13C>G	p.Pro5Ala	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.13C>G	p.Pro5Ala	missense	Exon 1 of 3	ENSP00000297290.3	O95415-1
BRI3	ENST00000539286.5	TSL:2	c.13C>G	p.Pro5Ala	missense	Exon 1 of 3	ENSP00000440936.1	O95415-2
BRI3	ENST00000456357.6	TSL:2	n.151-543C>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000134

AC:

AN:

149316

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000487

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.0000134

AC:

AN:

149316

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

72800

show subpopulations

African (AFR)

AF:

0.0000487

AC:

AN:

41068

American (AMR)

AF:

0.00

AC:

AN:

15018

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

5080

South Asian (SAS)

AF:

0.00

AC:

AN:

4804

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9840

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

66824

Other (OTH)

AF:

0.00

AC:

AN:

2052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.000142

Hom.:

Bravo

AF:

0.0000151

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

Benign

0.15

BayesDel_addAF

Benign

-0.076

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.90

DEOGEN2

Benign

0.063

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

M_CAP

Pathogenic

0.85

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.0

PhyloP100

5.6

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.22

Sift

Benign

0.035

Sift4G

Uncertain

0.036

Polyphen

1.0

Vest4

0.45

MutPred

0.47

Gain of helix (P = 0.0078)

MVP

0.45

MPC

0.35

ClinPred

0.67

GERP RS

3.0

PromoterAI

0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.9

Varity_R

0.17

gMVP

0.48

Mutation Taster

=53/47

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over