Variant 15-83263108-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001717.4(BNC1):c.2143A>G(p.Ile715Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

BNC1
NM_001717.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.24

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:

ENSG00000259986 (HGNC:):

ENSG00000259986 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06119448).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BNC1	NM_001717.4 linkuse as main transcript	c.2143A>G	p.Ile715Val	missense_variant	4/5	ENST00000345382.7	NP_001708.3	Q01954
BNC1	NM_001301206.2 linkuse as main transcript	c.2122A>G	p.Ile708Val	missense_variant	4/5		NP_001288135.1	Q01954F5GY04B7Z885
BNC1	XM_011521893.2 linkuse as main transcript	c.2068A>G	p.Ile690Val	missense_variant	4/5		XP_011520195.1
BNC1	XM_011521894.1 linkuse as main transcript	c.1789A>G	p.Ile597Val	missense_variant	3/4		XP_011520196.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
BNC1	ENST00000345382.7 linkuse as main transcript	c.2143A>G	p.Ile715Val	missense_variant	4/5	1	NM_001717.4	ENSP00000307041.2	Q01954
BNC1	ENST00000569704.2 linkuse as main transcript	c.2122A>G	p.Ile708Val	missense_variant	4/5	5		ENSP00000456727.1	F5GY04
ENSG00000259986	ENST00000565495.1 linkuse as main transcript	n.264+78040T>C		intron_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 18, 2023

The c.2143A>G (p.I715V) alteration is located in exon 4 (coding exon 4) of the BNC1 gene. This alteration results from a A to G substitution at nucleotide position 2143, causing the isoleucine (I) at amino acid position 715 to be replaced by a valine (V). 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

0.065

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.070

T;T

Eigen

Benign

-0.22

Eigen_PC

Benign

0.010

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.78

T;T

M_CAP

Benign

0.0069

MetaRNN

Benign

0.061

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;.

PrimateAI

Benign

0.33

PROVEAN

Benign

0.12

N;N

REVEL

Benign

0.080

Sift

Benign

0.65

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.0

B;B

Vest4

0.092

MutPred

0.37

Gain of loop (P = 0.1073);.;

MVP

0.068

MPC

0.12

ClinPred

0.62

GERP RS

5.5

Varity_R

0.034

gMVP

0.13

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over