8-54458520-C-CAG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_022454.4(SOX17):c.307+75_307+76insAG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 1,558,862 control chromosomes in the GnomAD database, including 35,924 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (3367 hom., cov: 30)
  • Exomes 𝑓: 0.20 (32557 hom.)
• Consequence: SOX17 NM_022454.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.690

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 8-54458520-C-CAG is Benign according to our data. Variant chr8-54458520-C-CAG is described in ClinVar as [Benign]. Clinvar id is 1259489.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.397 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX17	NM_022454.4	c.307+75_307+76insAG		intron_variant		ENST00000297316.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX17	ENST00000297316.5	c.307+75_307+76insAG		intron_variant		1	NM_022454.4	P1

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29916 AN: 152106 Hom.: 3368 Cov.: 30

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.274

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.183

GnomAD4 exome AF: 0.204 AC: 286543 AN: 1406638 Hom.: 32557 AF XY: 0.207 AC XY: 144738 AN XY: 698858

Gnomad4 AFR exome AF: 0.146

Gnomad4 AMR exome AF: 0.391

Gnomad4 ASJ exome AF: 0.145

Gnomad4 EAS exome AF: 0.386

Gnomad4 SAS exome AF: 0.363

Gnomad4 FIN exome AF: 0.225

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.203

GnomAD4 genome AF: 0.197 AC: 29929 AN: 152224 Hom.: 3367 Cov.: 30 AF XY: 0.204 AC XY: 15142 AN XY: 74394

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.275

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.411

Gnomad4 SAS AF: 0.381

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.180

Alfa AF: 0.187 Hom.: 319

Bravo AF: 0.200

Asia WGS AF: 0.352 AC: 1229 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

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Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs71554162; hg19: chr8-55371080;