rs11259905

Variant names:

• chr15-83280999-A-C
• rs11259905
• NM_001717.4:c.99+3531T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-83280999-A-C
• chr15-83280999-A-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.99+3531T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 152,112 control chromosomes in the GnomAD database, including 4,915 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 0.24 (4915 hom., cov: 32)
• Consequence: BNC1 NM_001717.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• Publications: 7 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=-0.6).
• 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.99+3531T>G		intron_variant	Intron 1 of 4	ENST00000345382.7	NP_001708.3
BNC1	NM_001301206.2	c.78+2136T>G		intron_variant	Intron 1 of 4		NP_001288135.1
BNC1	XM_011521893.2	c.24+2102T>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.99+3531T>G		intron_variant	Intron 1 of 4	1	NM_001717.4	ENSP00000307041.2
BNC1	ENST00000569704.2	c.78+2136T>G		intron_variant	Intron 1 of 4	5		ENSP00000456727.1
ENSG00000259986	ENST00000565495.1	n.264+95931A>C		intron_variant	Intron 1 of 1	5

Frequencies

GnomAD3 genomes AF: 0.243 AC: 36901 AN: 151994 Hom.: 4909 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.236

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.137

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.207

Gnomad OTH AF: 0.218

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

GnomAD4 genome AF: 0.243 AC: 36958 AN: 152112 Hom.: 4915 Cov.: 32 AF XY: 0.236 AC XY: 17551 AN XY: 74380

African (AFR) AF: 0.348 AC: 14445 AN: 41458

American (AMR) AF: 0.236 AC: 3610 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.262 AC: 909 AN: 3472

East Asian (EAS) AF: 0.137 AC: 709 AN: 5178

South Asian (SAS) AF: 0.151 AC: 725 AN: 4812

European-Finnish (FIN) AF: 0.176 AC: 1862 AN: 10596

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.207 AC: 14046 AN: 67998

Other (OTH) AF: 0.219 AC: 462 AN: 2114

Alfa AF: 0.160 Hom.: 392

Bravo AF: 0.254

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.3
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: rs11259905; hg19: chr15-83949751;