Variant 1-177276219-A-C 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_021165.4(BRINP2):c.797A>C(p.Glu266Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,612,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

BRINP2
NM_021165.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.82

Variant links:

Genes affected

BRINP2 (HGNC:13746): (BMP/retinoic acid inducible neural specific 2) Predicted to be involved in cellular response to retinoic acid; negative regulation of mitotic cell cycle; and positive regulation of neuron differentiation. Predicted to be located in extracellular region. Predicted to be active in dendrite; endoplasmic reticulum; and neuronal cell body. Implicated in oral squamous cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

BRINP2 links:

BRINP2 (HGNC:):

BRINP2 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=0.13138604).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BRINP2	NM_021165.4 linkuse as main transcript	c.797A>C	p.Glu266Ala	missense_variant	6/8	ENST00000361539.5	NP_066988.1	Q9C0B6-1
BRINP2	XM_005245379.3 linkuse as main transcript	c.797A>C	p.Glu266Ala	missense_variant	7/9		XP_005245436.1	Q9C0B6-1
BRINP2	XM_024448722.2 linkuse as main transcript	c.797A>C	p.Glu266Ala	missense_variant	7/9		XP_024304490.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BRINP2	ENST00000361539.5 linkuse as main transcript	c.797A>C	p.Glu266Ala	missense_variant	6/8	1	NM_021165.4	ENSP00000354481.4		Q9C0B6-1
BRINP2	ENST00000478325.1 linkuse as main transcript	n.653A>C		non_coding_transcript_exon_variant	3/5	2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000398

AC:

AN:

250978

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135726

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000882

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000102

AC:

149

AN:

1460696

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

726422

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000125

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000107

Hom.:

Bravo

AF:

0.0000567

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Mar 02, 2023

The c.797A>C (p.E266A) alteration is located in exon 6 (coding exon 5) of the BRINP2 gene. This alteration results from a A to C substitution at nucleotide position 797, causing the glutamic acid (E) at amino acid position 266 to be replaced by an alanine (A). 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

Benign

0.083

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.20

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.0087

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.47

M_CAP

Benign

0.0055

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.052

Sift

Benign

0.12

Sift4G

Benign

0.20

Polyphen

0.0080

Vest4

0.27

MVP

0.043

MPC

0.28

ClinPred

0.11

GERP RS

6.1

Varity_R

0.20

gMVP

0.48

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