9-113360674-A-G

Variant names:

• chr9-113360674-A-G
• rs752757
• NM_017688.3:c.468A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_017688.3(BSPRY):​c.468A>G​(p.Lys156Lys) 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
• Publications: 17 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017688.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSPRY	NM_017688.3	MANE Select	c.468A>G	p.Lys156Lys	synonymous	Exon 3 of 6	NP_060158.2
	BSPRY	NM_001317943.2		c.468A>G	p.Lys156Lys	synonymous	Exon 3 of 6	NP_001304872.1
	BSPRY	NM_001317944.2		c.468A>G	p.Lys156Lys	synonymous	Exon 3 of 5	NP_001304873.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	BSPRY	ENST00000374183.5	TSL:1 MANE Select	c.468A>G	p.Lys156Lys	synonymous	Exon 3 of 6	ENSP00000363298.4
	BSPRY	ENST00000462085.1	TSL:1	n.506A>G		non_coding_transcript_exon	Exon 3 of 5

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

GnomAD2 exomes AF: 0.263 AC: 62259 AN: 237162 AF XY: 0.256

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 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

African (AFR) AF: 0.499 AC: 16651 AN: 33338

American (AMR) AF: 0.350 AC: 15290 AN: 43644

Ashkenazi Jewish (ASJ) AF: 0.266 AC: 6898 AN: 25916

East Asian (EAS) AF: 0.444 AC: 17528 AN: 39496

South Asian (SAS) AF: 0.278 AC: 23574 AN: 84820

European-Finnish (FIN) AF: 0.118 AC: 6263 AN: 52910

Middle Eastern (MID) AF: 0.315 AC: 1404 AN: 4464

European-Non Finnish (NFE) AF: 0.217 AC: 240189 AN: 1109362

Other (OTH) AF: 0.265 AC: 15918 AN: 60006

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

African (AFR) AF: 0.485 AC: 20110 AN: 41480

American (AMR) AF: 0.329 AC: 5031 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 912 AN: 3470

East Asian (EAS) AF: 0.398 AC: 2049 AN: 5152

South Asian (SAS) AF: 0.285 AC: 1372 AN: 4814

European-Finnish (FIN) AF: 0.119 AC: 1260 AN: 10602

Middle Eastern (MID) AF: 0.303 AC: 89 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14723 AN: 67932

Other (OTH) AF: 0.309 AC: 654 AN: 2114

Alfa AF: 0.244 Hom.: 14483

Bravo AF: 0.328

Asia WGS AF: 0.339 AC: 1178 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	12
DANN	Benign	0.62
PhyloP100		1.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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