2-5692535-T-C

Position:

• chr2-5692535-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003108.4(SOX11):​c.-187T>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 0.816 in 476,996 control chromosomes in the GnomAD database, including 160,657 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (53833 hom., cov: 23)
  • Exomes 𝑓: 0.80 (106824 hom.)
• Consequence: SOX11 NM_003108.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0840

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-5692535-T-C is Benign according to our data. Variant chr2-5692535-T-C is described in ClinVar as [Benign]. Clinvar id is 1177695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SOX11	NM_003108.4	c.-187T>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.-187T>C		5_prime_UTR_variant	1/1		NM_003108.4	P1

Frequencies

GnomAD3 genomes AF: 0.846 AC: 126098 AN: 149074 Hom.: 53773 Cov.: 23

Gnomad AFR AF: 0.960

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.858

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.930

Gnomad FIN AF: 0.846

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.845

GnomAD4 exome AF: 0.803 AC: 263155 AN: 327820 Hom.: 106824 AF XY: 0.802 AC XY: 134232 AN XY: 167402

Gnomad4 AFR exome AF: 0.956

Gnomad4 AMR exome AF: 0.876

Gnomad4 ASJ exome AF: 0.810

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.908

Gnomad4 FIN exome AF: 0.825

Gnomad4 NFE exome AF: 0.762

Gnomad4 OTH exome AF: 0.818

GnomAD4 genome AF: 0.846 AC: 126209 AN: 149176 Hom.: 53833 Cov.: 23 AF XY: 0.853 AC XY: 62002 AN XY: 72650

Gnomad4 AFR AF: 0.960

Gnomad4 AMR AF: 0.858

Gnomad4 ASJ AF: 0.829

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.931

Gnomad4 FIN AF: 0.846

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.846

Alfa AF: 0.725 Hom.: 2330

Bravo AF: 0.851

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 08, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	17
DANN	Benign	0.70

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6721975; hg19: chr2-5832667;