2-5692574-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003108.4(SOX11):c.-148G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 649,534 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (37 hom., cov: 30)
  • Exomes 𝑓: 0.024 (204 hom.)
• Consequence: SOX11 NM_003108.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.35

Genes affected

SOX11 (HGNC:11191): (SRY-box transcription factor 11) This intronless 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. The protein may function in the developing nervous system and play a role in tumorigenesis. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 2-5692574-G-C is Benign according to our data. Variant chr2-5692574-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1210901.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2915/151748) while in subpopulation NFE AF= 0.0292 (1979/67816). AF 95% confidence interval is 0.0281. There are 37 homozygotes in gnomad4. There are 1367 alleles in male gnomad4 subpopulation. Median coverage is 30. This position pass quality control queck.
• BS2: High AC in GnomAd at 2916 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX11	NM_003108.4	c.-148G>C		5_prime_UTR_variant	1/1	ENST00000322002.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SOX11	ENST00000322002.5	c.-148G>C		5_prime_UTR_variant	1/1		NM_003108.4	P1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2916 AN: 151640 Hom.: 37 Cov.: 30

Gnomad AFR AF: 0.00489

Gnomad AMI AF: 0.0297

Gnomad AMR AF: 0.0192

Gnomad ASJ AF: 0.0298

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00561

Gnomad FIN AF: 0.0217

Gnomad MID AF: 0.0321

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0226

GnomAD4 exome AF: 0.0244 AC: 12170 AN: 497786 Hom.: 204 AF XY: 0.0236 AC XY: 6081 AN XY: 257920

Gnomad4 AFR exome AF: 0.00375

Gnomad4 AMR exome AF: 0.0169

Gnomad4 ASJ exome AF: 0.0285

Gnomad4 EAS exome AF: 0.0000993

Gnomad4 SAS exome AF: 0.00891

Gnomad4 FIN exome AF: 0.0262

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.0264

GnomAD4 genome AF: 0.0192 AC: 2915 AN: 151748 Hom.: 37 Cov.: 30 AF XY: 0.0184 AC XY: 1367 AN XY: 74162

Gnomad4 AFR AF: 0.00487

Gnomad4 AMR AF: 0.0191

Gnomad4 ASJ AF: 0.0298

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00541

Gnomad4 FIN AF: 0.0217

Gnomad4 NFE AF: 0.0292

Gnomad4 OTH AF: 0.0224

Alfa AF: 0.00605 Hom.: 3

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 07, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
Cadd	Benign	19
Dann	Benign	0.84

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs186010692; hg19: chr2-5832706;