Variant chr21-46602231-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000291700.9(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
ENST00000291700.9 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.530

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 made for transcript

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
S100B	NM_006272.3 linkuse as main transcript	c.138+47A>G		intron_variant		ENST00000291700.9	NP_006263.1
S100B	XM_017028424.3 linkuse as main transcript	c.138+47A>G		intron_variant			XP_016883913.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
S100B	ENST00000291700.9 linkuse as main transcript	c.138+47A>G	intron_variant	1	NM_006272.3	ENSP00000291700	P1
S100B	ENST00000367071.4 linkuse as main transcript	c.138+47A>G	intron_variant	1		ENSP00000356038
S100B	ENST00000397648.1 linkuse as main transcript	c.138+47A>G	intron_variant	1		ENSP00000380769	P1

Frequencies

GnomAD3 genomes

AF:

0.0965

AC:

14672

AN:

152092

Hom.:

926

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.116

AC:

27073

AN:

234090

Hom.:

2138

AF XY:

0.116

AC XY:

14632

AN XY:

126180

show subpopulations

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 SAS exome

AF:

0.101

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.:

AF XY:

0.104

AC XY:

72950

AN XY:

702244

show subpopulations

Gnomad4 AFR exome

AF:

0.0470

Gnomad4 AMR exome

AF:

0.0679

Gnomad4 ASJ exome

AF:

0.135

Gnomad4 EAS exome

AF:

0.349

Gnomad4 SAS exome

AF:

0.0979

Gnomad4 FIN exome

AF:

0.113

Gnomad4 NFE exome

AF:

0.0962

Gnomad4 OTH exome

AF:

0.113

GnomAD4 genome

AF:

0.0964

AC:

14677

AN:

152210

Hom.:

926

Cov.:

AF XY:

0.0984

AC XY:

7322

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0488

Gnomad4 AMR

AF:

0.0933

Gnomad4 ASJ

AF:

0.135

Gnomad4 EAS

AF:

0.337

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.114

Gnomad4 NFE

AF:

0.101

Gnomad4 OTH

AF:

0.111

Alfa

AF:

0.103

Hom.:

889

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over