15-83272982-G-C

Variant names:

• chr15-83272982-G-C
• rs11852287
• NM_001717.4:c.100-4750C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001717.4(BNC1):​c.100-4750C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 151,976 control chromosomes in the GnomAD database, including 5,296 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5296 hom., cov: 32)
• Consequence: BNC1 NM_001717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.355
• Publications: 4 publications found

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 Gene-Disease associations (from GenCC):

• premature ovarian failure 16

  Inheritance: Unknown, AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 46 XX gonadal dysgenesis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000259986 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
BNC1	NM_001717.4	c.100-4750C>G		intron_variant	Intron 1 of 4	ENST00000345382.7	NP_001708.3
BNC1	NM_001301206.2	c.79-4750C>G		intron_variant	Intron 1 of 4		NP_001288135.1
BNC1	XM_011521893.2	c.25-4750C>G		intron_variant	Intron 1 of 4		XP_011520195.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BNC1	ENST00000345382.7	c.100-4750C>G		intron_variant	Intron 1 of 4	1	NM_001717.4	ENSP00000307041.2
BNC1	ENST00000569704.2	c.79-4750C>G		intron_variant	Intron 1 of 4	5		ENSP00000456727.1
ENSG00000259986	ENST00000565495.1	n.264+87914G>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38558 AN: 151858 Hom.: 5289 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.138

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.197

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.231

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.254 AC: 38616 AN: 151976 Hom.: 5296 Cov.: 32 AF XY: 0.246 AC XY: 18291 AN XY: 74288

African (AFR) AF: 0.349 AC: 14436 AN: 41402

American (AMR) AF: 0.244 AC: 3723 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1008 AN: 3468

East Asian (EAS) AF: 0.138 AC: 715 AN: 5170

South Asian (SAS) AF: 0.154 AC: 742 AN: 4810

European-Finnish (FIN) AF: 0.197 AC: 2077 AN: 10562

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.224 AC: 15227 AN: 67976

Other (OTH) AF: 0.230 AC: 485 AN: 2108

Alfa AF: 0.127 Hom.: 206

Bravo AF: 0.264

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.36
DANN	Benign	0.52
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11852287; hg19: chr15-83941734;