rs2296074

Positions:

• chr9-113368445-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017688.3(BSPRY):​c.682+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 1,579,148 control chromosomes in the GnomAD database, including 3,103 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 0.047 (261 hom., cov: 32)
  • Exomes 𝑓: 0.058 (2842 hom.)
• Consequence: BSPRY NM_017688.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

Genes affected

BSPRY (HGNC:18232): (B-box and SPRY domain containing) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to act upstream of or within cellular response to leukemia inhibitory factor. Predicted to be located in cell leading edge; membrane; and perinuclear region of cytoplasm. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BSPRY	NM_017688.3	c.682+62T>C		intron_variant		ENST00000374183.5	NP_060158.2
BSPRY	NM_001317943.2	c.697+62T>C		intron_variant			NP_001304872.1
BSPRY	NM_001317944.2	c.558-1171T>C		intron_variant			NP_001304873.1
BSPRY	XM_006717149.4	c.679+62T>C		intron_variant			XP_006717212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BSPRY	ENST00000374183.5	c.682+62T>C		intron_variant		1	NM_017688.3	ENSP00000363298	P1
BSPRY	ENST00000462085.1	n.596-1171T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.0465 AC: 7070 AN: 151890 Hom.: 262 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0462

Gnomad AMR AF: 0.0487

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.0847

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0351

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0559

Gnomad OTH AF: 0.0658

GnomAD4 exome AF: 0.0577 AC: 82295 AN: 1427140 Hom.: 2842 AF XY: 0.0595 AC XY: 42133 AN XY: 707624

Gnomad4 AFR exome AF: 0.0107

Gnomad4 AMR exome AF: 0.0416

Gnomad4 ASJ exome AF: 0.146

Gnomad4 EAS exome AF: 0.0895

Gnomad4 SAS exome AF: 0.103

Gnomad4 FIN exome AF: 0.0402

Gnomad4 NFE exome AF: 0.0535

Gnomad4 OTH exome AF: 0.0642

GnomAD4 genome AF: 0.0465 AC: 7073 AN: 152008 Hom.: 261 Cov.: 32 AF XY: 0.0461 AC XY: 3427 AN XY: 74312

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0488

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.0846

Gnomad4 SAS AF: 0.110

Gnomad4 FIN AF: 0.0351

Gnomad4 NFE AF: 0.0559

Gnomad4 OTH AF: 0.0656

Alfa AF: 0.0544 Hom.: 61

Bravo AF: 0.0464

Asia WGS AF: 0.123 AC: 427 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.78

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

Other links and lift over

dbSNP: rs2296074; hg19: chr9-116130725;