21-46602317-C-G

Variant names:

• chr21-46602317-C-G
• rs1051169
• NM_006272.3:c.99G>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006272.3(S100B):​c.99G>C​(p.Leu33Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,612,876 control chromosomes in the GnomAD database, including 357,102 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 0.60 (28516 hom., cov: 32)
  • Exomes 𝑓: 0.67 (328586 hom.)
• Consequence: S100B NM_006272.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 38 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP7: Synonymous conserved (PhyloP=-2.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100B	NM_006272.3	c.99G>C	p.Leu33Leu	synonymous_variant	Exon 2 of 3	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3	c.99G>C	p.Leu33Leu	synonymous_variant	Exon 2 of 3		XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100B	ENST00000291700.9	c.99G>C	p.Leu33Leu	synonymous_variant	Exon 2 of 3	1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4	c.99G>C	p.Leu33Leu	synonymous_variant	Exon 2 of 4	1		ENSP00000356038.4
S100B	ENST00000397648.1	c.99G>C	p.Leu33Leu	synonymous_variant	Exon 1 of 2	1		ENSP00000380769.1

Frequencies

GnomAD3 genomes AF: 0.600 AC: 91198 AN: 151918 Hom.: 28504 Cov.: 32

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.654

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.616

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.630

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.538

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.591

GnomAD2 exomes AF: 0.652 AC: 163805 AN: 251260 AF XY: 0.653

Gnomad AFR exome AF: 0.416

Gnomad AMR exome AF: 0.758

Gnomad ASJ exome AF: 0.611

Gnomad EAS exome AF: 0.559

Gnomad FIN exome AF: 0.698

Gnomad NFE exome AF: 0.668

Gnomad OTH exome AF: 0.650

GnomAD4 exome AF: 0.668 AC: 975892 AN: 1460840 Hom.: 328586 Cov.: 38 AF XY: 0.667 AC XY: 485021 AN XY: 726770

African (AFR) AF: 0.406 AC: 13580 AN: 33446

American (AMR) AF: 0.753 AC: 33642 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 16073 AN: 26126

East Asian (EAS) AF: 0.551 AC: 21882 AN: 39696

South Asian (SAS) AF: 0.633 AC: 54603 AN: 86210

European-Finnish (FIN) AF: 0.692 AC: 36978 AN: 53416

Middle Eastern (MID) AF: 0.568 AC: 3276 AN: 5766

European-Non Finnish (NFE) AF: 0.681 AC: 756639 AN: 1111126

Other (OTH) AF: 0.650 AC: 39219 AN: 60366

GnomAD4 genome AF: 0.600 AC: 91249 AN: 152036 Hom.: 28516 Cov.: 32 AF XY: 0.605 AC XY: 44962 AN XY: 74328

African (AFR) AF: 0.419 AC: 17367 AN: 41442

American (AMR) AF: 0.691 AC: 10559 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 2133 AN: 3464

East Asian (EAS) AF: 0.562 AC: 2901 AN: 5166

South Asian (SAS) AF: 0.630 AC: 3031 AN: 4808

European-Finnish (FIN) AF: 0.694 AC: 7338 AN: 10572

Middle Eastern (MID) AF: 0.534 AC: 157 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45927 AN: 67978

Other (OTH) AF: 0.588 AC: 1240 AN: 2110

Alfa AF: 0.647 Hom.: 10295

Bravo AF: 0.592

Asia WGS AF: 0.568 AC: 1978 AN: 3478

EpiCase AF: 0.668

EpiControl AF: 0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	0.59
DANN	Benign	0.41
PhyloP100		-2.5
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: rs1051169; hg19: chr21-48022230; COSMIC: COSV52452647;