NM_006272.3:c.139-452C>T

Variant names:

• chr21-46599955-G-A
• rs881827
• NM_006272.3:c.139-452C>T

Variant summary

Our verdict is Benign. Variant got -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

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100B	NM_006272.3	c.139-452C>T		intron_variant	Intron 2 of 2	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3	c.139-452C>T		intron_variant	Intron 2 of 2		XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100B	ENST00000291700.9	c.139-452C>T		intron_variant	Intron 2 of 2	1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4	c.232+327C>T		intron_variant	Intron 3 of 3	1		ENSP00000356038.4
S100B	ENST00000397648.1	c.139-452C>T		intron_variant	Intron 1 of 1	1		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

Gnomad4 AFR AF: 0.252

Gnomad4 AMR AF: 0.317

Gnomad4 ASJ AF: 0.145

Gnomad4 EAS AF: 0.313

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.226

Gnomad4 NFE AF: 0.299

Gnomad4 OTH AF: 0.255

Alfa AF: 0.286 Hom.: 6503

Bravo AF: 0.284

Asia WGS AF: 0.297 AC: 1039 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.061
DANN	Benign	0.40

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: rs881827; hg19: chr21-48019868;