15-83258068-T-C

Position:

chr15-83258068-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001717.4(BNC1):c.2359A>G(p.Ser787Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00237 in 1,612,248 control chromosomes in the GnomAD database, including 96 homozygotes. 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 Benign (★★).

Frequency

Genomes: 𝑓 0.013 ( 48 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 48 hom. )

Consequence

BNC1
NM_001717.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.313

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021147132).

BP6

Variant 15-83258068-T-C is Benign according to our data. Variant chr15-83258068-T-C is described in ClinVar as [Benign]. Clinvar id is 770625.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0126 (1924/152340) while in subpopulation AFR AF= 0.045 (1872/41578). AF 95% confidence interval is 0.0433. There are 48 homozygotes in gnomad4. There are 928 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1924 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
BNC1	NM_001717.4 linkuse as main transcript	c.2359A>G	p.Ser787Gly	missense_variant	5/5	ENST00000345382.7
BNC1	NM_001301206.2 linkuse as main transcript	c.2338A>G	p.Ser780Gly	missense_variant	5/5
BNC1	XM_011521893.2 linkuse as main transcript	c.2284A>G	p.Ser762Gly	missense_variant	5/5
BNC1	XM_011521894.1 linkuse as main transcript	c.2005A>G	p.Ser669Gly	missense_variant	4/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
BNC1	ENST00000345382.7 linkuse as main transcript	c.2359A>G	p.Ser787Gly	missense_variant	5/5	1	NM_001717.4
	ENST00000565495.1 linkuse as main transcript	n.264+73000T>C		intron_variant, non_coding_transcript_variant		5
BNC1	ENST00000569704.2 linkuse as main transcript	c.2338A>G	p.Ser780Gly	missense_variant	5/5	5		P1

Frequencies

GnomAD3 genomes

AF:

0.0126

AC:

1918

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0450

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00242

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00717

GnomAD3 exomes

AF:

0.00317

AC:

797

AN:

251266

Hom.:

AF XY:

0.00213

AC XY:

289

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.0458

Gnomad AMR exome

AF:

0.00121

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:

0.0000440

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00130

AC:

1891

AN:

1459908

Hom.:

Cov.:

AF XY:

0.00111

AC XY:

803

AN XY:

725800

show subpopulations

Gnomad4 AFR exome

AF:

0.0492

Gnomad4 AMR exome

AF:

0.00152

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.00234

GnomAD4 genome

AF:

0.0126

AC:

1924

AN:

152340

Hom.:

Cov.:

AF XY:

0.0125

AC XY:

928

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.0450

Gnomad4 AMR

AF:

0.00242

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00710

Alfa

AF:

0.00221

Hom.:

Bravo

AF:

0.0141

ESP6500AA

AF:

0.0436

AC:

192

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00428

AC:

519

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 30, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.93

DANN

Benign

0.70

DEOGEN2

Benign

0.10

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.56

T;T

MetaRNN

Benign

0.0021

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.20

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.91

N;N

REVEL

Benign

0.031

Sift

Benign

0.66

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0

B;B

Vest4

0.039

MVP

0.11

MPC

0.13

ClinPred

0.00073

GERP RS

0.050

Varity_R

0.071

gMVP

0.18

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