21-46599326-G-A

Variant names:

• chr21-46599326-G-A
• rs9722
• NM_006272.3:c.*37C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 53 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006272.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100B	NM_006272.3	MANE Select	c.*37C>T		3_prime_UTR	Exon 3 of 3	NP_006263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100B	ENST00000291700.9	TSL:1 MANE Select	c.*37C>T		3_prime_UTR	Exon 3 of 3	ENSP00000291700.4
	S100B	ENST00000367071.4	TSL:1	c.*125C>T		3_prime_UTR	Exon 4 of 4	ENSP00000356038.4
	S100B	ENST00000397648.1	TSL:1	c.*37C>T		3_prime_UTR	Exon 2 of 2	ENSP00000380769.1

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

GnomAD2 exomes AF: 0.157 AC: 38687 AN: 246542 AF XY: 0.154

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 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

African (AFR) AF: 0.425 AC: 13881 AN: 32656

American (AMR) AF: 0.0932 AC: 4010 AN: 43006

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 3568 AN: 25922

East Asian (EAS) AF: 0.349 AC: 13835 AN: 39590

South Asian (SAS) AF: 0.191 AC: 16146 AN: 84640

European-Finnish (FIN) AF: 0.131 AC: 6970 AN: 53314

Middle Eastern (MID) AF: 0.156 AC: 890 AN: 5702

European-Non Finnish (NFE) AF: 0.0990 AC: 109065 AN: 1101616

Other (OTH) AF: 0.151 AC: 9012 AN: 59802

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

African (AFR) AF: 0.406 AC: 16854 AN: 41486

American (AMR) AF: 0.142 AC: 2168 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 478 AN: 3466

East Asian (EAS) AF: 0.340 AC: 1760 AN: 5170

South Asian (SAS) AF: 0.217 AC: 1045 AN: 4822

European-Finnish (FIN) AF: 0.135 AC: 1431 AN: 10592

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.105 AC: 7111 AN: 68000

Other (OTH) AF: 0.209 AC: 442 AN: 2112

Alfa AF: 0.146 Hom.: 1601

Bravo AF: 0.215

Asia WGS AF: 0.301 AC: 1042 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.24
DANN	Benign	0.67
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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