rs9722

Positions:

• chr21-46599326-G-A

Variant summary

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

The NM_006272.3(S100B):​c.*37C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,598,392 control chromosomes in the GnomAD database, including 19,105 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 0.21 (4636 hom., cov: 33)
  • Exomes 𝑓: 0.12 (14469 hom.)
• Consequence: S100B NM_006272.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S100B	NM_006272.3	c.*37C>T		3_prime_UTR_variant	3/3	ENST00000291700.9
S100B	XM_017028424.3	c.*37C>T		3_prime_UTR_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S100B	ENST00000291700.9	c.*37C>T		3_prime_UTR_variant	3/3	1	NM_006272.3	P1
S100B	ENST00000367071.4	c.*125C>T		3_prime_UTR_variant	4/4	1
S100B	ENST00000397648.1	c.*37C>T		3_prime_UTR_variant	2/2	1		P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31442 AN: 152026 Hom.: 4615 Cov.: 33

Gnomad AFR AF: 0.406

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.142

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.135

Gnomad MID AF: 0.196

Gnomad NFE AF: 0.105

Gnomad OTH AF: 0.206

GnomAD3 exomes AF: 0.157 AC: 38687 AN: 246542 Hom.: 4158 AF XY: 0.154 AC XY: 20520 AN XY: 133172

Gnomad AFR exome AF: 0.412

Gnomad AMR exome AF: 0.0879

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.333

Gnomad SAS exome AF: 0.195

Gnomad FIN exome AF: 0.132

Gnomad NFE exome AF: 0.110

Gnomad OTH exome AF: 0.138

GnomAD4 exome AF: 0.123 AC: 177377 AN: 1446248 Hom.: 14469 Cov.: 29 AF XY: 0.124 AC XY: 89309 AN XY: 719628

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.0932

Gnomad4 ASJ exome AF: 0.138

Gnomad4 EAS exome AF: 0.349

Gnomad4 SAS exome AF: 0.191

Gnomad4 FIN exome AF: 0.131

Gnomad4 NFE exome AF: 0.0990

Gnomad4 OTH exome AF: 0.151

GnomAD4 genome AF: 0.207 AC: 31514 AN: 152144 Hom.: 4636 Cov.: 33 AF XY: 0.208 AC XY: 15460 AN XY: 74382

Gnomad4 AFR AF: 0.406

Gnomad4 AMR AF: 0.142

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.135

Gnomad4 NFE AF: 0.105

Gnomad4 OTH AF: 0.209

Alfa AF: 0.144 Hom.: 1134

Bravo AF: 0.215

Asia WGS AF: 0.301 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs9722; hg19: chr21-48019239; COSMIC: COSV52452941;