ENST00000397648.1:c.-193C>T

Variant names:

• chr21-46602608-G-A
• rs11911834
• ENST00000397648.1:c.-193C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000397648.1(S100B):​c.-193C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000166 in 541,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000015 (0 hom.)
• Consequence: S100B ENST00000397648.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 5 publications found

Genes affected

S100B (HGNC:10500): (S100 calcium binding protein B) The protein encoded by this gene is a member of the S100 family of proteins containing 2 EF-hand calcium-binding motifs. S100 proteins are localized in the cytoplasm and/or nucleus of a wide range of cells, and involved in the regulation of a number of cellular processes such as cell cycle progression and differentiation. S100 genes include at least 13 members which are located as a cluster on chromosome 1q21; however, this gene is located at 21q22.3. This protein may function in Neurite extension, proliferation of melanoma cells, stimulation of Ca2+ fluxes, inhibition of PKC-mediated phosphorylation, astrocytosis and axonal proliferation, and inhibition of microtubule assembly. Chromosomal rearrangements and altered expression of this gene have been implicated in several neurological, neoplastic, and other types of diseases, including Alzheimer's disease, Down's syndrome, epilepsy, amyotrophic lateral sclerosis, melanoma, and type I diabetes. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100B	NM_006272.3	c.-1-192C>T		intron_variant	Intron 1 of 2	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3	c.-8-185C>T		intron_variant	Intron 1 of 2		XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100B	ENST00000397648.1	c.-193C>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1		ENSP00000380769.1
S100B	ENST00000397648.1	c.-193C>T		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000380769.1
S100B	ENST00000291700.9	c.-1-192C>T		intron_variant	Intron 1 of 2	1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4	c.-1-192C>T		intron_variant	Intron 1 of 3	1		ENSP00000356038.4

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152064 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000154 AC: 6 AN: 389544 Hom.: 0 Cov.: 5 AF XY: 0.00000978 AC XY: 2 AN XY: 204426

African (AFR) AF: 0.00 AC: 0 AN: 10826

American (AMR) AF: 0.00 AC: 0 AN: 12278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11970

East Asian (EAS) AF: 0.00 AC: 0 AN: 26902

South Asian (SAS) AF: 0.0000932 AC: 3 AN: 32200

European-Finnish (FIN) AF: 0.0000815 AC: 2 AN: 24526

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1780

European-Non Finnish (NFE) AF: 0.00000406 AC: 1 AN: 246442

Other (OTH) AF: 0.00 AC: 0 AN: 22620

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152064 Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3 AN XY: 74284

African (AFR) AF: 0.0000484 AC: 2 AN: 41360

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 1

Bravo AF: 0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.96
DANN	Benign	0.67
PhyloP100		-0.32
PromoterAI		0.0024	Neutral

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

Other links and lift over

dbSNP: rs11911834; hg19: chr21-48022521;