Variant 6-36328609-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001010903.5(BNIP5):c.716A>G(p.Lys239Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

BNIP5
NM_001010903.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.94

Variant links:

Genes affected

BNIP5 (HGNC:33769): (BCL2 interacting protein 5)

BNIP5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02705115).

BP6

Variant 6-36328609-T-C is Benign according to our data. Variant chr6-36328609-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3134680.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNIP5	NM_001010903.5 linkuse as main transcript	c.716A>G	p.Lys239Arg	missense_variant	3/12	ENST00000437635.3	NP_001010903.3
BNIP5	XM_011514596.3 linkuse as main transcript	c.716A>G	p.Lys239Arg	missense_variant	3/12		XP_011512898.1	P0C671
BNIP5	XM_011514597.3 linkuse as main transcript	c.716A>G	p.Lys239Arg	missense_variant	3/12		XP_011512899.1
BNIP5	XM_011514598.3 linkuse as main transcript	c.-29A>G		5_prime_UTR_variant	2/11		XP_011512900.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BNIP5	ENST00000437635.3 linkuse as main transcript	c.716A>G	p.Lys239Arg	missense_variant	3/12	1	NM_001010903.5	ENSP00000418983.1		P0C671

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251486

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

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:

0.00

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459858

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726432

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.0060

DANN

Benign

0.23

DEOGEN2

Benign

0.0057

Eigen

Benign

-2.0

Eigen_PC

Benign

-2.1

FATHMM_MKL

Benign

0.0031

LIST_S2

Benign

0.30

M_CAP

Benign

0.0012

MetaRNN

Benign

0.027

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.83

PROVEAN

Benign

0.26

REVEL

Benign

0.049

Sift

Benign

1.0

Sift4G

Benign

0.89

Polyphen

0.0

Vest4

0.062

MutPred

0.17

Loss of loop (P = 0.0022);

MVP

0.014

MPC

0.013

ClinPred

0.036

GERP RS

-8.2

Varity_R

0.028

gMVP

0.024

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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