21-46601141-C-T

Position:

• chr21-46601141-C-T

Variant summary

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

The NM_006272.3(S100B):​c.138+1137G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.644 in 152,000 control chromosomes in the GnomAD database, including 31,975 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 0.64 (31975 hom., cov: 32)
• Consequence: S100B NM_006272.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.774

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.716 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100B	NM_006272.3	c.138+1137G>A		intron_variant		ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3	c.138+1137G>A		intron_variant			XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100B	ENST00000291700.9	c.138+1137G>A		intron_variant		1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4	c.139-766G>A		intron_variant		1		ENSP00000356038.4
S100B	ENST00000397648.1	c.138+1137G>A		intron_variant		1		ENSP00000380769.1

Frequencies

GnomAD3 genomes AF: 0.644 AC: 97810 AN: 151882 Hom.: 31958 Cov.: 32

Gnomad AFR AF: 0.550

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.710

Gnomad ASJ AF: 0.606

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.678

Gnomad OTH AF: 0.627

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

GnomAD4 genome AF: 0.644 AC: 97877 AN: 152000 Hom.: 31975 Cov.: 32 AF XY: 0.649 AC XY: 48242 AN XY: 74288

Gnomad4 AFR AF: 0.550

Gnomad4 AMR AF: 0.711

Gnomad4 ASJ AF: 0.606

Gnomad4 EAS AF: 0.565

Gnomad4 SAS AF: 0.737

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.678

Gnomad4 OTH AF: 0.629

Alfa AF: 0.664 Hom.: 53271

Bravo AF: 0.637

Asia WGS AF: 0.646 AC: 2248 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.41
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: rs2300403; hg19: chr21-48021054;