chr21-46602608-G-T

Variant names:

• chr21-46602608-G-T
• rs11911834
• ENST00000397648.1:c.-193C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000397648.1(S100B):​c.-193C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 541,620 control chromosomes in the GnomAD database, including 1,110 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 0.061 (741 hom., cov: 33)
  • Exomes 𝑓: 0.018 (369 hom.)
• Consequence: S100B ENST00000397648.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.183 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100B	NM_006272.3	c.-1-192C>A		intron_variant	Intron 1 of 2	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3	c.-8-185C>A		intron_variant	Intron 1 of 2		XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
S100B	ENST00000397648.1	c.-193C>A		5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000380769.1
S100B	ENST00000291700.9	c.-1-192C>A		intron_variant	Intron 1 of 2	1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4	c.-1-192C>A		intron_variant	Intron 1 of 3	1		ENSP00000356038.4

Frequencies

GnomAD3 genomes AF: 0.0607 AC: 9234 AN: 152036 Hom.: 735 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0267

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00329

Gnomad OTH AF: 0.0502

GnomAD4 exome AF: 0.0178 AC: 6941 AN: 389466 Hom.: 369 Cov.: 5 AF XY: 0.0205 AC XY: 4199 AN XY: 204372

African (AFR) AF: 0.183 AC: 1981 AN: 10812

American (AMR) AF: 0.0208 AC: 255 AN: 12278

Ashkenazi Jewish (ASJ) AF: 0.00301 AC: 36 AN: 11970

East Asian (EAS) AF: 0.00108 AC: 29 AN: 26902

South Asian (SAS) AF: 0.0860 AC: 2766 AN: 32162

European-Finnish (FIN) AF: 0.0170 AC: 416 AN: 24516

Middle Eastern (MID) AF: 0.0292 AC: 52 AN: 1780

European-Non Finnish (NFE) AF: 0.00335 AC: 825 AN: 246430

Other (OTH) AF: 0.0257 AC: 581 AN: 22616

GnomAD4 genome AF: 0.0609 AC: 9259 AN: 152154 Hom.: 741 Cov.: 33 AF XY: 0.0613 AC XY: 4562 AN XY: 74400

African (AFR) AF: 0.186 AC: 7722 AN: 41460

American (AMR) AF: 0.0266 AC: 407 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3470

East Asian (EAS) AF: 0.00444 AC: 23 AN: 5184

South Asian (SAS) AF: 0.108 AC: 522 AN: 4824

European-Finnish (FIN) AF: 0.0203 AC: 215 AN: 10596

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00329 AC: 224 AN: 68014

Other (OTH) AF: 0.0554 AC: 117 AN: 2112

Alfa AF: 0.00256 Hom.: 1

Bravo AF: 0.0647

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.44
DANN	Benign	0.50
PhyloP100		-0.32
PromoterAI		-0.066	Neutral
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: rs11911834; hg19: chr21-48022521; COSMIC: COSV52452904;