Genetic Variant NM_022454.4:c.308-146C>A (chr8-54458912-C-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_022454.4(SOX17):c.308-146C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 707,512 control chromosomes in the GnomAD database, including 5,391 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.12 ( 1246 hom., cov: 34)

Exomes 𝑓: 0.11 ( 4145 hom. )

Consequence

SOX17
NM_022454.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.35

Publications

1 publications found

Variant links:

Genes affected

SOX17 (HGNC:18122): (SRY-box transcription factor 17) This gene encodes a member of the SOX (SRY-related HMG-box) family of transcription factors involved in the regulation of embryonic development and in the determination of the cell fate. The encoded protein may act as a transcriptional regulator after forming a protein complex with other proteins. [provided by RefSeq, Jul 2008]

SOX17 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
vesicoureteral reflux 3
Inheritance: AD Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
familial vesicoureteral reflux
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SOX17 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 8-54458912-C-A is Benign according to our data. Variant chr8-54458912-C-A is described in ClinVar as [Benign]. Clinvar id is 1222886.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOX17	NM_022454.4 link	c.308-146C>A		intron_variant	Intron 1 of 1	ENST00000297316.5	NP_071899.1	Q9H6I2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOX17	ENST00000297316.5 link	c.308-146C>A		intron_variant	Intron 1 of 1	1	NM_022454.4	ENSP00000297316.4		Q9H6I2

Frequencies

GnomAD3 genomes

AF:

0.117

AC:

17736

AN:

152074

Hom.:

1238

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.152

Gnomad ASJ

AF:

0.0510

Gnomad EAS

AF:

0.327

Gnomad SAS

AF:

0.0952

Gnomad FIN

AF:

0.131

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.0919

Gnomad OTH

AF:

0.110

GnomAD4 exome

AF:

0.108

AC:

60004

AN:

555320

Hom.:

4145

AF XY:

0.107

AC XY:

30536

AN XY:

285496

show subpopulations

African (AFR)

AF:

0.124

AC:

1512

AN:

12204

American (AMR)

AF:

0.165

AC:

2537

AN:

15386

Ashkenazi Jewish (ASJ)

AF:

0.0475

AC:

639

AN:

13466

East Asian (EAS)

AF:

0.318

AC:

8804

AN:

27678

South Asian (SAS)

AF:

0.0927

AC:

4047

AN:

43650

European-Finnish (FIN)

AF:

0.123

AC:

3665

AN:

29866

Middle Eastern (MID)

AF:

0.0724

AC:

155

AN:

2142

European-Non Finnish (NFE)

AF:

0.0926

AC:

35340

AN:

381802

Other (OTH)

AF:

0.113

AC:

3305

AN:

29126

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

2870

5741

8611

11482

14352

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.117

AC:

17765

AN:

152192

Hom.:

1246

Cov.:

AF XY:

0.119

AC XY:

8871

AN XY:

74394

show subpopulations

African (AFR)

AF:

0.124

AC:

5172

AN:

41558

American (AMR)

AF:

0.153

AC:

2333

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0510

AC:

177

AN:

3472

East Asian (EAS)

AF:

0.327

AC:

1678

AN:

5128

South Asian (SAS)

AF:

0.0947

AC:

457

AN:

4826

European-Finnish (FIN)

AF:

0.131

AC:

1390

AN:

10594

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0919

AC:

6252

AN:

67996

Other (OTH)

AF:

0.115

AC:

244

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

805

1610

2414

3219

4024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.100

Hom.:

105

Bravo

AF:

0.120

Asia WGS

AF:

0.227

AC:

787

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

May 15, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.1

(source)

DANN

Benign

0.54

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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NM_022454.4:c.308-146C>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over