rs2186358

Variant names:

• chr21-46602462-C-A
• rs2186358
• ENST00000397648.1:c.-47G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397648.1(S100B):​c.-47G>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 0.782 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_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 21 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
S100B	NM_006272.3	c.-1-46G>T		intron_variant	Intron 1 of 2	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3	c.-8-39G>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.-47G>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1		ENSP00000380769.1
S100B	ENST00000397648.1	c.-47G>T		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000380769.1
S100B	ENST00000291700.9	c.-1-46G>T		intron_variant	Intron 1 of 2	1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4	c.-1-46G>T		intron_variant	Intron 1 of 3	1		ENSP00000356038.4

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

GnomAD2 exomes AF: 0.793 AC: 185045 AN: 233228 AF XY: 0.796

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 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

African (AFR) AF: 0.649 AC: 20908 AN: 32234

American (AMR) AF: 0.832 AC: 33304 AN: 40048

Ashkenazi Jewish (ASJ) AF: 0.744 AC: 18403 AN: 24750

East Asian (EAS) AF: 0.902 AC: 35681 AN: 39576

South Asian (SAS) AF: 0.823 AC: 68228 AN: 82906

European-Finnish (FIN) AF: 0.821 AC: 42816 AN: 52134

Middle Eastern (MID) AF: 0.717 AC: 4030 AN: 5624

European-Non Finnish (NFE) AF: 0.780 AC: 856037 AN: 1098094

Other (OTH) AF: 0.787 AC: 46650 AN: 59258

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

African (AFR) AF: 0.654 AC: 27121 AN: 41462

American (AMR) AF: 0.811 AC: 12404 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.741 AC: 2572 AN: 3472

East Asian (EAS) AF: 0.903 AC: 4672 AN: 5174

South Asian (SAS) AF: 0.845 AC: 4064 AN: 4812

European-Finnish (FIN) AF: 0.828 AC: 8750 AN: 10574

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.779 AC: 52931 AN: 67990

Other (OTH) AF: 0.756 AC: 1598 AN: 2114

Alfa AF: 0.765 Hom.: 125719

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
PhyloP100		-2.6
PromoterAI		-0.016	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2186358; hg19: chr21-48022375;