9-113360674-A-G

Position:

• chr9-113360674-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017688.3(BSPRY):​c.468A>G​(p.Lys156=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 1,606,006 control chromosomes in the GnomAD database, including 52,617 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 0.31 (8344 hom., cov: 32)
  • Exomes 𝑓: 0.24 (44273 hom.)
• Consequence: BSPRY NM_017688.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP7: Synonymous conserved (PhyloP=1.08 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
BSPRY	NM_017688.3	c.468A>G	p.Lys156=	synonymous_variant	3/6	ENST00000374183.5
BSPRY	NM_001317943.2	c.468A>G	p.Lys156=	synonymous_variant	3/6
BSPRY	NM_001317944.2	c.468A>G	p.Lys156=	synonymous_variant	3/5
BSPRY	XM_006717149.4	c.468A>G	p.Lys156=	synonymous_variant	3/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
BSPRY	ENST00000374183.5	c.468A>G	p.Lys156=	synonymous_variant	3/6	1	NM_017688.3	P1
BSPRY	ENST00000462085.1	n.506A>G		non_coding_transcript_exon_variant	3/5	1

Frequencies

GnomAD3 genomes AF: 0.305 AC: 46354 AN: 151932 Hom.: 8300 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.330

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.285

Gnomad FIN AF: 0.119

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.309

GnomAD3 exomes AF: 0.263 AC: 62259 AN: 237162 Hom.: 9302 AF XY: 0.256 AC XY: 32895 AN XY: 128736

Gnomad AFR exome AF: 0.489

Gnomad AMR exome AF: 0.355

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.397

Gnomad SAS exome AF: 0.274

Gnomad FIN exome AF: 0.118

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.236 AC: 343715 AN: 1453956 Hom.: 44273 Cov.: 35 AF XY: 0.237 AC XY: 171085 AN XY: 722652

Gnomad4 AFR exome AF: 0.499

Gnomad4 AMR exome AF: 0.350

Gnomad4 ASJ exome AF: 0.266

Gnomad4 EAS exome AF: 0.444

Gnomad4 SAS exome AF: 0.278

Gnomad4 FIN exome AF: 0.118

Gnomad4 NFE exome AF: 0.217

Gnomad4 OTH exome AF: 0.265

GnomAD4 genome AF: 0.306 AC: 46456 AN: 152050 Hom.: 8344 Cov.: 32 AF XY: 0.304 AC XY: 22570 AN XY: 74338

Gnomad4 AFR AF: 0.485

Gnomad4 AMR AF: 0.329

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.285

Gnomad4 FIN AF: 0.119

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.309

Alfa AF: 0.243 Hom.: 9449

Bravo AF: 0.328

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.62

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

LitVar

Other links and lift over

dbSNP: rs752757; hg19: chr9-116122954; COSMIC: COSV65242599;