Variant chr15-83263285-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001717.4(BNC1):c.1966C>T(p.His656Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000167 in 1,614,212 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

BNC1
NM_001717.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.80

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 Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.047588736).

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BNC1	NM_001717.4 linkuse as main transcript	c.1966C>T	p.His656Tyr	missense_variant	4/5	ENST00000345382.7
BNC1	NM_001301206.2 linkuse as main transcript	c.1945C>T	p.His649Tyr	missense_variant	4/5
BNC1	XM_011521893.2 linkuse as main transcript	c.1891C>T	p.His631Tyr	missense_variant	4/5
BNC1	XM_011521894.1 linkuse as main transcript	c.1612C>T	p.His538Tyr	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BNC1	ENST00000345382.7 linkuse as main transcript	c.1966C>T	p.His656Tyr	missense_variant	4/5	1	NM_001717.4
	ENST00000565495.1 linkuse as main transcript	n.264+78217G>A		intron_variant, non_coding_transcript_variant		5
BNC1	ENST00000569704.2 linkuse as main transcript	c.1945C>T	p.His649Tyr	missense_variant	4/5	5		P1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152204

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:

0.000828

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000199

AC:

AN:

251278

Hom.:

AF XY:

0.000265

AC XY:

AN XY:

135844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000173

AC:

253

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000187

AC XY:

136

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000812

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000112

AC:

AN:

152322

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000181

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.000206

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000296

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

Sep 17, 2021

The c.1966C>T (p.H656Y) alteration is located in exon 4 (coding exon 4) of the BNC1 gene. This alteration results from a C to T substitution at nucleotide position 1966, causing the histidine (H) at amino acid position 656 to be replaced by a tyrosine (Y). 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

0.068

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.58

CADD

Benign

9.0

DANN

Uncertain

0.98

DEOGEN2

Benign

0.22

T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.59

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-2.1

N;N

REVEL

Benign

0.058

Sift

Benign

0.13

T;T

Sift4G

Benign

0.35

T;T

Polyphen

0.10

B;B

Vest4

0.10

MVP

0.043

MPC

0.19

ClinPred

0.042

GERP RS

3.9

Varity_R

0.056

gMVP

0.14

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