chr21-46602231-T-C

Variant names:

• chr21-46602231-T-C
• rs2839356
• NM_006272.3:c.138+47A>G

Variant summary

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

The NM_006272.3(S100B):​c.138+47A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 1,561,054 control chromosomes in the GnomAD database, including 9,996 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 0.096 (926 hom., cov: 33)
  • Exomes 𝑓: 0.10 (9070 hom.)
• Consequence: S100B NM_006272.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 8 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=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100B	NM_006272.3	c.138+47A>G		intron_variant	Intron 2 of 2	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3	c.138+47A>G		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.138+47A>G		intron_variant	Intron 2 of 2	1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4	c.138+47A>G		intron_variant	Intron 2 of 3	1		ENSP00000356038.4
S100B	ENST00000397648.1	c.138+47A>G		intron_variant	Intron 1 of 1	1		ENSP00000380769.1

Frequencies

GnomAD3 genomes AF: 0.0965 AC: 14672 AN: 152092 Hom.: 926 Cov.: 33

Gnomad AFR AF: 0.0487

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.0934

Gnomad ASJ AF: 0.135

Gnomad EAS AF: 0.336

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.131

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.113

GnomAD2 exomes AF: 0.116 AC: 27073 AN: 234090 AF XY: 0.116

Gnomad AFR exome AF: 0.0487

Gnomad AMR exome AF: 0.0659

Gnomad ASJ exome AF: 0.140

Gnomad EAS exome AF: 0.334

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.106

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.103 AC: 145741 AN: 1408844 Hom.: 9070 Cov.: 22 AF XY: 0.104 AC XY: 72950 AN XY: 702244

African (AFR) AF: 0.0470 AC: 1508 AN: 32112

American (AMR) AF: 0.0679 AC: 2848 AN: 41954

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 3312 AN: 24582

East Asian (EAS) AF: 0.349 AC: 13743 AN: 39406

South Asian (SAS) AF: 0.0979 AC: 8043 AN: 82194

European-Finnish (FIN) AF: 0.113 AC: 5924 AN: 52576

Middle Eastern (MID) AF: 0.125 AC: 696 AN: 5586

European-Non Finnish (NFE) AF: 0.0962 AC: 103100 AN: 1072110

Other (OTH) AF: 0.113 AC: 6567 AN: 58324

GnomAD4 genome AF: 0.0964 AC: 14677 AN: 152210 Hom.: 926 Cov.: 33 AF XY: 0.0984 AC XY: 7322 AN XY: 74412

African (AFR) AF: 0.0488 AC: 2027 AN: 41548

American (AMR) AF: 0.0933 AC: 1426 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.135 AC: 468 AN: 3470

East Asian (EAS) AF: 0.337 AC: 1740 AN: 5168

South Asian (SAS) AF: 0.108 AC: 519 AN: 4824

European-Finnish (FIN) AF: 0.114 AC: 1213 AN: 10600

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.101 AC: 6848 AN: 67996

Other (OTH) AF: 0.111 AC: 234 AN: 2110

Alfa AF: 0.100 Hom.: 1107

Bravo AF: 0.0943

Asia WGS AF: 0.205 AC: 710 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.2
DANN	Benign	0.61
PhyloP100		0.53
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2839356; hg19: chr21-48022144; COSMIC: COSV52453713;