Variant 21-46602317-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_006272.3(S100B):c.99G>C(p.Leu33Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.662 in 1,612,876 control chromosomes in the GnomAD database, including 357,102 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 0.60 ( 28516 hom., cov: 32)

Exomes 𝑓: 0.67 ( 328586 hom. )

Consequence

S100B
NM_006272.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.54

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.63).

BP7

Synonymous conserved (PhyloP=-2.54 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.68 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.99G>C	p.Leu33Leu	synonymous_variant	2/3	ENST00000291700.9	NP_006263.1	P04271A0A0S2Z4C5
S100B	XM_017028424.3 linkuse as main transcript	c.99G>C	p.Leu33Leu	synonymous_variant	2/3		XP_016883913.1	P04271A0A0S2Z4C5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
S100B	ENST00000291700.9 linkuse as main transcript	c.99G>C	p.Leu33Leu	synonymous_variant	2/3	1	NM_006272.3	ENSP00000291700.4	P04271
S100B	ENST00000367071.4 linkuse as main transcript	c.99G>C	p.Leu33Leu	synonymous_variant	2/4	1		ENSP00000356038.4	A8MRB1
S100B	ENST00000397648.1 linkuse as main transcript	c.99G>C	p.Leu33Leu	synonymous_variant	1/2	1		ENSP00000380769.1	P04271

Frequencies

GnomAD3 genomes

AF:

0.600

AC:

91198

AN:

151918

Hom.:

28504

Cov.:

show subpopulations

Gnomad AFR

AF:

0.419

Gnomad AMI

AF:

0.654

Gnomad AMR

AF:

0.690

Gnomad ASJ

AF:

0.616

Gnomad EAS

AF:

0.562

Gnomad SAS

AF:

0.630

Gnomad FIN

AF:

0.694

Gnomad MID

AF:

0.538

Gnomad NFE

AF:

0.676

Gnomad OTH

AF:

0.591

GnomAD3 exomes

AF:

0.652

AC:

163805

AN:

251260

Hom.:

54306

AF XY:

0.653

AC XY:

88685

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.416

Gnomad AMR exome

AF:

0.758

Gnomad ASJ exome

AF:

0.611

Gnomad EAS exome

AF:

0.559

Gnomad SAS exome

AF:

0.636

Gnomad FIN exome

AF:

0.698

Gnomad NFE exome

AF:

0.668

Gnomad OTH exome

AF:

0.650

GnomAD4 exome

AF:

0.668

AC:

975892

AN:

1460840

Hom.:

328586

Cov.:

AF XY:

0.667

AC XY:

485021

AN XY:

726770

show subpopulations

Gnomad4 AFR exome

AF:

0.406

Gnomad4 AMR exome

AF:

0.753

Gnomad4 ASJ exome

AF:

0.615

Gnomad4 EAS exome

AF:

0.551

Gnomad4 SAS exome

AF:

0.633

Gnomad4 FIN exome

AF:

0.692

Gnomad4 NFE exome

AF:

0.681

Gnomad4 OTH exome

AF:

0.650

GnomAD4 genome

AF:

0.600

AC:

91249

AN:

152036

Hom.:

28516

Cov.:

AF XY:

0.605

AC XY:

44962

AN XY:

74328

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.691

Gnomad4 ASJ

AF:

0.616

Gnomad4 EAS

AF:

0.562

Gnomad4 SAS

AF:

0.630

Gnomad4 FIN

AF:

0.694

Gnomad4 NFE

AF:

0.676

Gnomad4 OTH

AF:

0.588

Alfa

AF:

0.647

Hom.:

10295

Bravo

AF:

0.592

Asia WGS

AF:

0.568

AC:

1978

AN:

3478

EpiCase

AF:

0.668

EpiControl

AF:

0.658

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

0.59

DANN

Benign

0.41

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

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