Genetic Variant NM_017688.3:c.682+62T>C (chr9-113368445-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.183

Publications

4 publications found

Variant links:

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]

BSPRY links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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	Effect	Exon rank	MANE	Protein	UniProt
BSPRY	NM_017688.3 link	c.682+62T>C	intron_variant	Intron 5 of 5	ENST00000374183.5	NP_060158.2	Q5W0U4-1
BSPRY	NM_001317943.2 link	c.697+62T>C	intron_variant	Intron 5 of 5		NP_001304872.1	Q5W0U4
BSPRY	NM_001317944.2 link	c.558-1171T>C	intron_variant	Intron 4 of 4		NP_001304873.1	Q5W0U4-2
BSPRY	XM_006717149.4 link	c.679+62T>C	intron_variant	Intron 5 of 5		XP_006717212.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
BSPRY	ENST00000374183.5 link	c.682+62T>C		intron_variant	Intron 5 of 5	1	NM_017688.3	ENSP00000363298.4		Q5W0U4-1
BSPRY	ENST00000462085.1 link	n.596-1171T>C		intron_variant	Intron 4 of 4	1

Frequencies

GnomAD3 genomes

AF:

0.0465

AC:

7070

AN:

151890

Hom.:

262

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.0107

AC:

343

AN:

31932

American (AMR)

AF:

0.0416

AC:

1655

AN:

39746

Ashkenazi Jewish (ASJ)

AF:

0.146

AC:

3615

AN:

24740

East Asian (EAS)

AF:

0.0895

AC:

3510

AN:

39216

South Asian (SAS)

AF:

0.103

AC:

8471

AN:

82082

European-Finnish (FIN)

AF:

0.0402

AC:

2121

AN:

52726

Middle Eastern (MID)

AF:

0.0763

AC:

369

AN:

4836

European-Non Finnish (NFE)

AF:

0.0535

AC:

58439

AN:

1093120

Other (OTH)

AF:

0.0642

AC:

3772

AN:

58742

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

3734

7468

11202

14936

18670

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2230

4460

6690

8920

11150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0465

AC:

7073

AN:

152008

Hom.:

261

Cov.:

AF XY:

0.0461

AC XY:

3427

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.0114

AC:

473

AN:

41444

American (AMR)

AF:

0.0488

AC:

745

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.150

AC:

519

AN:

3466

East Asian (EAS)

AF:

0.0846

AC:

437

AN:

5168

South Asian (SAS)

AF:

0.110

AC:

531

AN:

4812

European-Finnish (FIN)

AF:

0.0351

AC:

371

AN:

10584

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0559

AC:

3799

AN:

67974

Other (OTH)

AF:

0.0656

AC:

138

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

332

663

995

1326

1658

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

184

276

368

460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0544

Hom.:

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

(source)

DANN

Benign

0.78

PhyloP100

-0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over