rs3006488

Positions:

• chr1-153390031-A-G
• chr1-153390031-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The 1-153390031-A-G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,323,982 control chromosomes in the GnomAD database, including 11,412 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 0.17 (2681 hom., cov: 32)
  • Exomes 𝑓: 0.12 (8731 hom.)
• Consequence: S100A8 ENST00000368733.4 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586

Genes affected

S100A8 (HGNC:10498): (S100 calcium binding protein A8) 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. This protein may function in the inhibition of casein kinase and as a cytokine. Altered expression of this protein is associated with the disease cystic fibrosis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.305 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A8	NM_002964.5			downstream_gene_variant		ENST00000368733.4	NP_002955.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100A8	ENST00000368733.4			downstream_gene_variant		1	NM_002964.5	ENSP00000357722	P1
S100A8	ENST00000368732.5			downstream_gene_variant		3		ENSP00000357721	P1

Frequencies

GnomAD3 genomes AF: 0.166 AC: 25185 AN: 152038 Hom.: 2670 Cov.: 32

Gnomad AFR AF: 0.309

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0949

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.0881

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.115

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.116 AC: 135567 AN: 1171826 Hom.: 8731 Cov.: 15 AF XY: 0.115 AC XY: 67230 AN XY: 584920

Gnomad4 AFR exome AF: 0.311

Gnomad4 AMR exome AF: 0.107

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.0913

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.0916

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.122

GnomAD4 genome AF: 0.166 AC: 25247 AN: 152156 Hom.: 2681 Cov.: 32 AF XY: 0.163 AC XY: 12120 AN XY: 74398

Gnomad4 AFR AF: 0.310

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.103

Gnomad4 EAS AF: 0.0945

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.0881

Gnomad4 NFE AF: 0.115

Gnomad4 OTH AF: 0.148

Alfa AF: 0.121 Hom.: 2642

Bravo AF: 0.174

Asia WGS AF: 0.101 AC: 352 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	2.1
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3006488; hg19: chr1-153362507; COSMIC: COSV64197946;