dbSNP rs2839357: S100B:c.-1-558T>C (chr21-46602974-A-G) – 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.-1-558T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 152,430 control chromosomes in the GnomAD database, including 951 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 0.098 ( 951 hom., cov: 32)

Exomes 𝑓: 0.12 ( 0 hom. )

Consequence

S100B
NM_006272.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.168

Publications

7 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.321 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100B	NM_006272.3 link	c.-1-558T>C		intron_variant	Intron 1 of 2	ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3 link	c.-8-551T>C		intron_variant	Intron 1 of 2		XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
S100B	ENST00000291700.9 link	c.-1-558T>C	intron_variant	Intron 1 of 2	1	NM_006272.3	ENSP00000291700.4
S100B	ENST00000367071.4 link	c.-1-558T>C	intron_variant	Intron 1 of 3	1		ENSP00000356038.4
S100B	ENST00000397648.1 link	c.-559T>C	upstream_gene_variant		1		ENSP00000380769.1

Frequencies

GnomAD3 genomes

AF:

0.0980

AC:

14911

AN:

152136

Hom.:

951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0487

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.0951

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.333

Gnomad SAS

AF:

0.107

Gnomad FIN

AF:

0.116

Gnomad MID

AF:

0.139

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.117

GnomAD4 exome

AF:

0.119

AC:

AN:

176

Hom.:

AF XY:

0.160

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AF:

0.0556

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AF:

0.100

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.127

AC:

AN:

142

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0980

AC:

14917

AN:

152254

Hom.:

951

Cov.:

AF XY:

0.0994

AC XY:

7403

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0488

AC:

2026

AN:

41558

American (AMR)

AF:

0.0950

AC:

1453

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

476

AN:

3470

East Asian (EAS)

AF:

0.334

AC:

1728

AN:

5174

South Asian (SAS)

AF:

0.107

AC:

518

AN:

4822

European-Finnish (FIN)

AF:

0.116

AC:

1233

AN:

10614

Middle Eastern (MID)

AF:

0.139

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

7035

AN:

67998

Other (OTH)

AF:

0.115

AC:

243

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

677

1354

2031

2708

3385

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

176

352

528

704

880

<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:

0.0993

Hom.:

488

Bravo

AF:

0.0954

Asia WGS

AF:

0.206

AC:

712

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

2.6

(source)

DANN

Benign

0.59

PhyloP100

-0.17

PromoterAI

0.020

Neutral

(source)

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over