rs2186358

Positions:

• chr21-46602462-C-A
• chr21-46602462-C-G
• chr21-46602462-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397648.1(S100B):​c.-47G>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 0.782 in 1,586,718 control chromosomes in the GnomAD database, including 487,182 homozygotes. 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 0.76 (44033 hom., cov: 32)
  • Exomes 𝑓: 0.78 (443149 hom.)
• Consequence: S100B ENST00000397648.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S100B	NM_006272.3	c.-1-46G>T		intron_variant		ENST00000291700.9
S100B	XM_017028424.3	c.-8-39G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S100B	ENST00000397648.1	c.-47G>T		5_prime_UTR_variant	1/2	1		P1
S100B	ENST00000291700.9	c.-1-46G>T		intron_variant		1	NM_006272.3	P1
S100B	ENST00000367071.4	c.-1-46G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115008 AN: 151974 Hom.: 44008 Cov.: 32

Gnomad AFR AF: 0.654

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.811

Gnomad ASJ AF: 0.741

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.844

Gnomad FIN AF: 0.828

Gnomad MID AF: 0.725

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.755

GnomAD3 exomes AF: 0.793 AC: 185045 AN: 233228 Hom.: 73792 AF XY: 0.796 AC XY: 100492 AN XY: 126286

Gnomad AFR exome AF: 0.654

Gnomad AMR exome AF: 0.834

Gnomad ASJ exome AF: 0.742

Gnomad EAS exome AF: 0.893

Gnomad SAS exome AF: 0.829

Gnomad FIN exome AF: 0.830

Gnomad NFE exome AF: 0.775

Gnomad OTH exome AF: 0.779

GnomAD4 exome AF: 0.785 AC: 1126057 AN: 1434624 Hom.: 443149 Cov.: 26 AF XY: 0.786 AC XY: 561578 AN XY: 714060

Gnomad4 AFR exome AF: 0.649

Gnomad4 AMR exome AF: 0.832

Gnomad4 ASJ exome AF: 0.744

Gnomad4 EAS exome AF: 0.902

Gnomad4 SAS exome AF: 0.823

Gnomad4 FIN exome AF: 0.821

Gnomad4 NFE exome AF: 0.780

Gnomad4 OTH exome AF: 0.787

GnomAD4 genome AF: 0.757 AC: 115087 AN: 152094 Hom.: 44033 Cov.: 32 AF XY: 0.764 AC XY: 56773 AN XY: 74344

Gnomad4 AFR AF: 0.654

Gnomad4 AMR AF: 0.811

Gnomad4 ASJ AF: 0.741

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.845

Gnomad4 FIN AF: 0.828

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.756

Alfa AF: 0.770 Hom.: 76489

Bravo AF: 0.750

Asia WGS AF: 0.852 AC: 2961 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.42
DANN	Benign	0.38

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.20		Position offset: -13

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

Publications

LitVar

Other links and lift over

dbSNP: rs2186358; hg19: chr21-48022375;