Genetic Variant SOX9-AS1:n.31+78_31+79delTG (chr17-72120683-GCA-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The ENST00000533232.5(SOX9-AS1):n.31+78_31+79delTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0152 in 150,776 control chromosomes in the GnomAD database, including 52 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.015 ( 52 hom., cov: 0)

Exomes 𝑓: 0.059 ( 0 hom. )

Consequence

SOX9-AS1
ENST00000533232.5 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.221

Publications

0 publications found

Variant links:

Genes affected

SOX9-AS1 (HGNC:49321): (SOX9 antisense RNA 1)

SOX9-AS1 links:

ENSG00000288605 (HGNC:):

ENSG00000288605 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 17-72120683-GCA-G is Benign according to our data. Variant chr17-72120683-GCA-G is described in ClinVar as Benign. ClinVar VariationId is 1284079.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0147 (2186/148930) while in subpopulation AFR AF = 0.0495 (2013/40694). AF 95% confidence interval is 0.0477. There are 52 homozygotes in GnomAd4. There are 1035 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 52 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000533232.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOX9-AS1	NR_103737.1		n.31+78_31+79delTG		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
SOX9-AS1	ENST00000533232.5	TSL:1	n.31+78_31+79delTG	intron	N/A
SOX9-AS1	ENST00000414600.1	TSL:3	n.96+21000_96+21001delTG	intron	N/A
ENSG00000288605	ENST00000628742.2	TSL:5	n.147-35640_147-35639delTG	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0147

AC:

2182

AN:

148840

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0495

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00586

Gnomad ASJ

AF:

0.000291

Gnomad EAS

AF:

0.000200

Gnomad SAS

AF:

0.00128

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0194

Gnomad NFE

AF:

0.000762

Gnomad OTH

AF:

0.00976

GnomAD4 exome

AF:

0.0590

AC:

109

AN:

1846

Hom.:

AF XY:

0.0621

AC XY:

AN XY:

854

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.134

AC:

AN:

American (AMR)

AF:

0.0417

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0909

AC:

AN:

154

East Asian (EAS)

AF:

0.0298

AC:

AN:

336

South Asian (SAS)

AF:

0.0556

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0611

AC:

AN:

1048

Other (OTH)

AF:

0.0435

AC:

AN:

138

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.294

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0147

AC:

2186

AN:

148930

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1035

AN XY:

72480

show subpopulations

African (AFR)

AF:

0.0495

AC:

2013

AN:

40694

American (AMR)

AF:

0.00586

AC:

AN:

15022

Ashkenazi Jewish (ASJ)

AF:

0.000291

AC:

AN:

3436

East Asian (EAS)

AF:

0.000201

AC:

AN:

4976

South Asian (SAS)

AF:

0.00129

AC:

AN:

4662

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9960

Middle Eastern (MID)

AF:

0.0210

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.000762

AC:

AN:

66930

Other (OTH)

AF:

0.00965

AC:

AN:

2072

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

104

208

311

415

519

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<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:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.22

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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17-72120683-GCACACACACA-GCACACACA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over