chr3-181712330-C-T
Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2
The NM_003106.4(SOX2):c.-31C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00468 in 1,341,842 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0045 ( 2 hom., cov: 32)
Exomes 𝑓: 0.0047 ( 21 hom. )
Consequence
SOX2
NM_003106.4 5_prime_UTR
NM_003106.4 5_prime_UTR
Scores
1
1
Clinical Significance
Conservation
PhyloP100: 0.417
Genes affected
SOX2 (HGNC:11195): (SRY-box transcription factor 2) This intronless gene encodes a member of the SRY-related HMG-box (SOX) family of transcription factors involved in the regulation of embryonic development and in the determination of cell fate. The product of this gene is required for stem-cell maintenance in the central nervous system, and also regulates gene expression in the stomach. Mutations in this gene have been associated with optic nerve hypoplasia and with syndromic microphthalmia, a severe form of structural eye malformation. This gene lies within an intron of another gene called SOX2 overlapping transcript (SOX2OT). [provided by RefSeq, Jul 2008]
SOX2-OT (HGNC:20209): (SOX2 overlapping transcript) This gene produces alternatively spliced long non-coding RNAs. These RNAs were observed to be upregulated in tumor cells and positively correlated to expression of the SRY-box 2 gene. Overexpression of these transcripts may promote cell proliferation. [provided by RefSeq, Dec 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -12 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.29).
BP6
?
Variant 3-181712330-C-T is Benign according to our data. Variant chr3-181712330-C-T is described in ClinVar as [Benign]. Clinvar id is 378636.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00454 (689/151672) while in subpopulation NFE AF= 0.00535 (363/67790). AF 95% confidence interval is 0.0049. There are 2 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd at 680 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SOX2 | NM_003106.4 | c.-31C>T | 5_prime_UTR_variant | 1/1 | ENST00000325404.3 | ||
SOX2-OT | NR_075091.1 | n.783-2855C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SOX2 | ENST00000325404.3 | c.-31C>T | 5_prime_UTR_variant | 1/1 | NM_003106.4 | P1 | |||
SOX2-OT | ENST00000626948.3 | n.837-2855C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00449 AC: 680AN: 151562Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00363 AC: 30AN: 8268Hom.: 0 AF XY: 0.00361 AC XY: 16AN XY: 4432
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GnomAD4 exome AF: 0.00470 AC: 5592AN: 1190170Hom.: 21 Cov.: 32 AF XY: 0.00467 AC XY: 2677AN XY: 573066
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 26, 2015 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at