Genetic Variant S100B:c.138+536A>G (chr21-46601742-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006272.3(S100B):c.138+536A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 152,100 control chromosomes in the GnomAD database, including 6,046 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 0.27 ( 6046 hom., cov: 33)

Consequence

S100B
NM_006272.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.457

Publications

8 publications found

Variant links:

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]

S100B links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.358 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100B	NM_006272.3 link	c.138+536A>G		intron_variant	Intron 2 of 2	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3 link	c.138+536A>G		intron_variant	Intron 2 of 2		XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
S100B	ENST00000291700.9 link	c.138+536A>G	intron_variant	Intron 2 of 2	1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4 link	c.138+536A>G	intron_variant	Intron 2 of 3	1		ENSP00000356038.4
S100B	ENST00000397648.1 link	c.138+536A>G	intron_variant	Intron 1 of 1	1		ENSP00000380769.1

Frequencies

GnomAD3 genomes

AF:

0.273

AC:

41505

AN:

151982

Hom.:

6037

Cov.:

show subpopulations

Gnomad AFR

AF:

0.362

Gnomad AMI

AF:

0.263

Gnomad AMR

AF:

0.214

Gnomad ASJ

AF:

0.307

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.239

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.288

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

GnomAD4 genome

AF:

0.273

AC:

41549

AN:

152100

Hom.:

6046

Cov.:

AF XY:

0.270

AC XY:

20083

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.362

AC:

15030

AN:

41468

American (AMR)

AF:

0.213

AC:

3264

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.307

AC:

1065

AN:

3468

East Asian (EAS)

AF:

0.352

AC:

1820

AN:

5172

South Asian (SAS)

AF:

0.170

AC:

821

AN:

4818

European-Finnish (FIN)

AF:

0.239

AC:

2528

AN:

10584

Middle Eastern (MID)

AF:

0.306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.237

AC:

16093

AN:

67986

Other (OTH)

AF:

0.284

AC:

599

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1522

3044

4566

6088

7610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

416

832

1248

1664

2080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.251

Hom.:

19097

Bravo

AF:

0.277

Asia WGS

AF:

0.262

AC:

909

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

2.8

(source)

DANN

Benign

0.68

PhyloP100

-0.46

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over