21-46599955-G-A

Variant names:

• chr21-46599955-G-A
• rs881827
• NM_006272.3:c.139-452C>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.139-452C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 152,074 control chromosomes in the GnomAD database, including 6,114 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 0.28 (6114 hom., cov: 33)
• Consequence: S100B NM_006272.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.648
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 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.139-452C>T		intron	N/A	NP_006263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100B	ENST00000291700.9	TSL:1 MANE Select	c.139-452C>T		intron	N/A	ENSP00000291700.4
	S100B	ENST00000367071.4	TSL:1	c.232+327C>T		intron	N/A	ENSP00000356038.4
	S100B	ENST00000397648.1	TSL:1	c.139-452C>T		intron	N/A	ENSP00000380769.1

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42353 AN: 151956 Hom.: 6108 Cov.: 33

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.221

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.313

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.299

Gnomad OTH AF: 0.255

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.279 AC: 42381 AN: 152074 Hom.: 6114 Cov.: 33 AF XY: 0.276 AC XY: 20496 AN XY: 74324

African (AFR) AF: 0.252 AC: 10436 AN: 41494

American (AMR) AF: 0.317 AC: 4840 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3466

East Asian (EAS) AF: 0.313 AC: 1620 AN: 5176

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4822

European-Finnish (FIN) AF: 0.226 AC: 2384 AN: 10550

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.299 AC: 20355 AN: 67986

Other (OTH) AF: 0.255 AC: 539 AN: 2110

Alfa AF: 0.287 Hom.: 11792

Bravo AF: 0.284

Asia WGS AF: 0.297 AC: 1039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.061
DANN	Benign	0.40
PhyloP100		-0.65
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: rs881827; hg19: chr21-48019868;