dbSNP rs28368064: SPO11:c.131+54G>A (chr20-57330052-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_012444.3(SPO11):c.131+54G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 1,506,254 control chromosomes in the GnomAD database, including 438 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 0.015 ( 18 hom., cov: 32)

Exomes 𝑓: 0.022 ( 420 hom. )

Consequence

SPO11
NM_012444.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.06

Publications

4 publications found

Variant links:

Genes affected

SPO11 (HGNC:11250): (SPO11 initiator of meiotic double strand breaks) Meiotic recombination and chromosome segregation require the formation of double-strand breaks (DSBs) in paired chromosome homologs. During meiosis in yeast, a meiotic recombination protein is covalently-linked to the 5' end of DSBs and is essential for the formation of DSBs. The protein encoded by this gene is similar in sequence and conserved features to the yeast meiotic recombination protein. The encoded protein belongs to the TOP6A protein family. Several transcript variants encoding different isoforms have been found for this gene, but the full-length nature of only two of them have been described. [provided by RefSeq, Jul 2008]

SPO11 links:

Genome browser will be placed here

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=-0.87).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0154 (2346/152348) while in subpopulation NFE AF = 0.0237 (1612/68028). AF 95% confidence interval is 0.0227. There are 18 homozygotes in GnomAd4. There are 1100 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPO11	NM_012444.3 link	c.131+54G>A		intron_variant	Intron 1 of 12	ENST00000371263.8	NP_036576.1	Q9Y5K1-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SPO11	ENST00000371263.8 link	c.131+54G>A	intron_variant	Intron 1 of 12	1	NM_012444.3	ENSP00000360310.3	Q9Y5K1-1
SPO11	ENST00000345868.8 link	c.131+54G>A	intron_variant	Intron 1 of 11	1		ENSP00000316034.4	Q9Y5K1-2
SPO11	ENST00000371260.8 link	c.131+54G>A	intron_variant	Intron 1 of 11	5		ENSP00000360307.4	Q5TCH7
SPO11	ENST00000418127.5 link	c.65+54G>A	intron_variant	Intron 1 of 9	3		ENSP00000413185.1	Q5TCH6

Frequencies

GnomAD3 genomes

AF:

0.0154

AC:

2345

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00456

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.00962

Gnomad ASJ

AF:

0.0130

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.0200

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0237

Gnomad OTH

AF:

0.0201

GnomAD4 exome

AF:

0.0224

AC:

30361

AN:

1353906

Hom.:

420

AF XY:

0.0225

AC XY:

14960

AN XY:

664010

show subpopulations

African (AFR)

AF:

0.00374

AC:

115

AN:

30728

American (AMR)

AF:

0.00981

AC:

322

AN:

32834

Ashkenazi Jewish (ASJ)

AF:

0.0171

AC:

400

AN:

23402

East Asian (EAS)

AF:

0.0000847

AC:

AN:

35416

South Asian (SAS)

AF:

0.0238

AC:

1818

AN:

76256

European-Finnish (FIN)

AF:

0.0223

AC:

777

AN:

34844

Middle Eastern (MID)

AF:

0.0215

AC:

AN:

4456

European-Non Finnish (NFE)

AF:

0.0243

AC:

25741

AN:

1059802

Other (OTH)

AF:

0.0194

AC:

1089

AN:

56168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

1446

2892

4339

5785

7231

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1000

2000

3000

4000

5000

<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:

0.0154

AC:

2346

AN:

152348

Hom.:

Cov.:

AF XY:

0.0148

AC XY:

1100

AN XY:

74500

show subpopulations

African (AFR)

AF:

0.00455

AC:

189

AN:

41584

American (AMR)

AF:

0.00960

AC:

147

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.0130

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.0178

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0200

AC:

212

AN:

10626

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0237

AC:

1612

AN:

68028

Other (OTH)

AF:

0.0198

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

116

231

347

462

578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

120

150

<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:

0.0204

Hom.:

Bravo

AF:

0.0139

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.73

(source)

DANN

Benign

0.86

PhyloP100

-3.1

PromoterAI

-0.040

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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