rs9984765

Positions:

• chr21-46601742-T-C
• chr21-46601742-T-A
• chr21-46601742-T-G

Variant summary

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

The NM_006272.3(S100B):​c.138+536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,100 control chromosomes in the GnomAD database, including 6,046 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 0.27 (6046 hom., cov: 33)
• Consequence: S100B NM_006272.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.457

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S100B	NM_006272.3	c.138+536A>G		intron_variant		ENST00000291700.9
S100B	XM_017028424.3	c.138+536A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S100B	ENST00000291700.9	c.138+536A>G		intron_variant		1	NM_006272.3	P1
S100B	ENST00000367071.4	c.138+536A>G		intron_variant		1
S100B	ENST00000397648.1	c.138+536A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.273 AC: 41505 AN: 151982 Hom.: 6037 Cov.: 33

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.307

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.170

Gnomad FIN AF: 0.239

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.273 AC: 41549 AN: 152100 Hom.: 6046 Cov.: 33 AF XY: 0.270 AC XY: 20083 AN XY: 74366

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.213

Gnomad4 ASJ AF: 0.307

Gnomad4 EAS AF: 0.352

Gnomad4 SAS AF: 0.170

Gnomad4 FIN AF: 0.239

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.284

Alfa AF: 0.247 Hom.: 8136

Bravo AF: 0.277

Asia WGS AF: 0.262 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.8
DANN	Benign	0.68

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: rs9984765; hg19: chr21-48021655;