Variant chr15-83262978-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM2PP5_ModerateBP4

The NM_001717.4(BNC1):c.2273C>T(p.Thr758Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,458,836 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 Likely pathogenic (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

BNC1
NM_001717.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 8.07

Variant links:

Genes affected

BNC1 (HGNC:1081): (basonuclin zinc finger protein 1) This gene encodes a zinc finger protein present in the basal cell layer of the epidermis and in hair follicles. It is also found in abundance in the germ cells of testis and ovary. This protein is thought to play a regulatory role in keratinocyte proliferation and it may also be a regulator for rRNA transcription. Disruption of this gene has been implicated in premature ovarian failure as well as testicular premature aging. [provided by RefSeq, Sep 2020]

BNC1 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-83262978-G-A is Pathogenic according to our data. Variant chr15-83262978-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 929778.Status of the report is criteria_provided_single_submitter, 1 stars.

BP4

Computational evidence support a benign effect (MetaRNN=0.17604735). . Strength limited to SUPPORTING due to the PP5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BNC1	NM_001717.4 linkuse as main transcript	c.2273C>T	p.Thr758Ile	missense_variant	4/5	ENST00000345382.7
BNC1	NM_001301206.2 linkuse as main transcript	c.2252C>T	p.Thr751Ile	missense_variant	4/5
BNC1	XM_011521893.2 linkuse as main transcript	c.2198C>T	p.Thr733Ile	missense_variant	4/5
BNC1	XM_011521894.1 linkuse as main transcript	c.1919C>T	p.Thr640Ile	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BNC1	ENST00000345382.7 linkuse as main transcript	c.2273C>T	p.Thr758Ile	missense_variant	4/5	1	NM_001717.4
	ENST00000565495.1 linkuse as main transcript	n.264+77910G>A		intron_variant, non_coding_transcript_variant		5
BNC1	ENST00000569704.2 linkuse as main transcript	c.2252C>T	p.Thr751Ile	missense_variant	4/5	5		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249234

Hom.:

AF XY:

0.00000743

AC XY:

AN XY:

134642

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1458836

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725222

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000594

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Premature ovarian failure

Pathogenic:1

Likely pathogenic, criteria provided, single submitter

research

Medical Cytogenetics and Molecular Genetics Laboratory, IRCCS Istituto Auxologico Italiano

Mar 02, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.064

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;T

Eigen

Benign

-0.044

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.024

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.2

M;.

MutationTaster

Benign

0.95

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.13

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

0.0030

B;B

Vest4

0.19

MutPred

0.46

Gain of catalytic residue at P760 (P = 0.0307);.;

MVP

0.16

MPC

0.41

ClinPred

0.84

GERP RS

3.7

Varity_R

0.10

gMVP

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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