8-54458594-C-T

Position:

• chr8-54458594-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_022454.4(SOX17):​c.307+149C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.198 in 945,688 control chromosomes in the GnomAD database, including 21,768 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2906 hom., cov: 33)
  • Exomes 𝑓: 0.20 (18862 hom.)
• Consequence: SOX17 NM_022454.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.898

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 8-54458594-C-T is Benign according to our data. Variant chr8-54458594-C-T is described in ClinVar as [Benign]. Clinvar id is 1265808.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	Protein	UniProt
SOX17	NM_022454.4	c.307+149C>T		intron_variant		ENST00000297316.5	NP_071899.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SOX17	ENST00000297316.5	c.307+149C>T		intron_variant		1	NM_022454.4	ENSP00000297316.4

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25611 AN: 152098 Hom.: 2909 Cov.: 33

Gnomad AFR AF: 0.0516

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.159

GnomAD4 exome AF: 0.204 AC: 162051 AN: 793472 Hom.: 18862 AF XY: 0.209 AC XY: 84234 AN XY: 403592

Gnomad4 AFR exome AF: 0.0465

Gnomad4 AMR exome AF: 0.352

Gnomad4 ASJ exome AF: 0.140

Gnomad4 EAS exome AF: 0.382

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.181

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.168 AC: 25605 AN: 152216 Hom.: 2906 Cov.: 33 AF XY: 0.177 AC XY: 13150 AN XY: 74398

Gnomad4 AFR AF: 0.0515

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.380

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.156

Alfa AF: 0.183 Hom.: 1672

Bravo AF: 0.168

Asia WGS AF: 0.344 AC: 1201 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.2
DANN	Benign	0.96

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

LitVar

Other links and lift over

dbSNP: rs12541742; hg19: chr8-55371154; COSMIC: COSV52027765;