rs2839357

Positions:

• chr21-46602974-A-G

Variant summary

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

The NM_006272.3(S100B):​c.-1-558T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 152,430 control chromosomes in the GnomAD database, including 951 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 0.098 (951 hom., cov: 32)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: S100B NM_006272.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.168

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100B	NM_006272.3	c.-1-558T>C		intron_variant		ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3	c.-8-551T>C		intron_variant			XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100B	ENST00000291700.9	c.-1-558T>C		intron_variant		1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4	c.-1-558T>C		intron_variant		1		ENSP00000356038.4

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14911 AN: 152136 Hom.: 951 Cov.: 32

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.0951

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.333

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.103

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.119 AC: 21 AN: 176 Hom.: 0 AF XY: 0.160 AC XY: 15 AN XY: 94

Gnomad4 AMR exome AF: 0.0556

Gnomad4 ASJ exome AF: 0.00

Gnomad4 SAS exome AF: 0.100

Gnomad4 NFE exome AF: 0.127

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.0980 AC: 14917 AN: 152254 Hom.: 951 Cov.: 32 AF XY: 0.0994 AC XY: 7403 AN XY: 74454

Gnomad4 AFR AF: 0.0488

Gnomad4 AMR AF: 0.0950

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.107

Gnomad4 FIN AF: 0.116

Gnomad4 NFE AF: 0.103

Gnomad4 OTH AF: 0.115

Alfa AF: 0.0998 Hom.: 448

Bravo AF: 0.0954

Asia WGS AF: 0.206 AC: 712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.59

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: rs2839357; hg19: chr21-48022887;