Variant 21-46602462-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000397648.1(S100B):c.-47G>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.782 in 1,586,718 control chromosomes in the GnomAD database, including 487,182 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 0.76 ( 44033 hom., cov: 32)

Exomes 𝑓: 0.78 ( 443149 hom. )

Consequence

S100B
ENST00000397648.1 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.56

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=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.881 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100B	NM_006272.3 link	c.-1-46G>T		intron_variant	Intron 1 of 2	ENST00000291700.9	NP_006263.1	P04271A0A0S2Z4C5
S100B	XM_017028424.3 link	c.-8-39G>T		intron_variant	Intron 1 of 2		XP_016883913.1	P04271A0A0S2Z4C5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
S100B	ENST00000397648.1 link	c.-47G>T	5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 2	1		ENSP00000380769.1	P04271
S100B	ENST00000397648.1 link	c.-47G>T	5_prime_UTR_variant	Exon 1 of 2	1		ENSP00000380769.1	P04271
S100B	ENST00000291700.9 link	c.-1-46G>T	intron_variant	Intron 1 of 2	1	NM_006272.3	ENSP00000291700.4	P04271
S100B	ENST00000367071.4 link	c.-1-46G>T	intron_variant	Intron 1 of 3	1		ENSP00000356038.4	A8MRB1

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

115008

AN:

151974

Hom.:

44008

Cov.:

show subpopulations

Gnomad AFR

AF:

0.654

Gnomad AMI

AF:

0.833

Gnomad AMR

AF:

0.811

Gnomad ASJ

AF:

0.741

Gnomad EAS

AF:

0.903

Gnomad SAS

AF:

0.844

Gnomad FIN

AF:

0.828

Gnomad MID

AF:

0.725

Gnomad NFE

AF:

0.779

Gnomad OTH

AF:

0.755

GnomAD3 exomes

AF:

0.793

AC:

185045

AN:

233228

Hom.:

73792

AF XY:

0.796

AC XY:

100492

AN XY:

126286

show subpopulations

Gnomad AFR exome

AF:

0.654

Gnomad AMR exome

AF:

0.834

Gnomad ASJ exome

AF:

0.742

Gnomad EAS exome

AF:

0.893

Gnomad SAS exome

AF:

0.829

Gnomad FIN exome

AF:

0.830

Gnomad NFE exome

AF:

0.775

Gnomad OTH exome

AF:

0.779

GnomAD4 exome

AF:

0.785

AC:

1126057

AN:

1434624

Hom.:

443149

Cov.:

AF XY:

0.786

AC XY:

561578

AN XY:

714060

show subpopulations

Gnomad4 AFR exome

AF:

0.649

Gnomad4 AMR exome

AF:

0.832

Gnomad4 ASJ exome

AF:

0.744

Gnomad4 EAS exome

AF:

0.902

Gnomad4 SAS exome

AF:

0.823

Gnomad4 FIN exome

AF:

0.821

Gnomad4 NFE exome

AF:

0.780

Gnomad4 OTH exome

AF:

0.787

GnomAD4 genome

AF:

0.757

AC:

115087

AN:

152094

Hom.:

44033

Cov.:

AF XY:

0.764

AC XY:

56773

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.654

Gnomad4 AMR

AF:

0.811

Gnomad4 ASJ

AF:

0.741

Gnomad4 EAS

AF:

0.903

Gnomad4 SAS

AF:

0.845

Gnomad4 FIN

AF:

0.828

Gnomad4 NFE

AF:

0.779

Gnomad4 OTH

AF:

0.756

Alfa

AF:

0.770

Hom.:

76489

Bravo

AF:

0.750

Asia WGS

AF:

0.852

AC:

2961

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.42

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.20

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.20

Position offset: -13

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