1-153390031-A-G

Variant names:

• chr1-153390031-A-G
• rs3006488
• NM_002964.5:c.*72T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368733.4(S100A8):​c.*72T>C 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
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000368733.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A8	NM_002964.5	MANE Select	c.*72T>C		downstream_gene	N/A	NP_002955.2
	S100A8	NM_001319196.1		c.*72T>C		downstream_gene	N/A	NP_001306125.1
	S100A8	NM_001319197.1		c.*72T>C		downstream_gene	N/A	NP_001306126.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A8	ENST00000368733.4	TSL:1 MANE Select	c.*72T>C		downstream_gene	N/A	ENSP00000357722.3
	S100A8	ENST00000477801.1	TSL:1	n.*173T>C		downstream_gene	N/A
	S100A8	ENST00000368732.5	TSL:3	c.*72T>C		downstream_gene	N/A	ENSP00000357721.1

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

African (AFR) AF: 0.311 AC: 8126 AN: 26132

American (AMR) AF: 0.107 AC: 3307 AN: 31014

Ashkenazi Jewish (ASJ) AF: 0.100 AC: 2018 AN: 20168

East Asian (EAS) AF: 0.0913 AC: 3452 AN: 37820

South Asian (SAS) AF: 0.104 AC: 7162 AN: 68984

European-Finnish (FIN) AF: 0.0916 AC: 4596 AN: 50168

Middle Eastern (MID) AF: 0.114 AC: 554 AN: 4880

European-Non Finnish (NFE) AF: 0.114 AC: 100281 AN: 883024

Other (OTH) AF: 0.122 AC: 6071 AN: 49636

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

African (AFR) AF: 0.310 AC: 12861 AN: 41498

American (AMR) AF: 0.121 AC: 1852 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3472

East Asian (EAS) AF: 0.0945 AC: 488 AN: 5162

South Asian (SAS) AF: 0.101 AC: 486 AN: 4814

European-Finnish (FIN) AF: 0.0881 AC: 935 AN: 10608

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.115 AC: 7814 AN: 67988

Other (OTH) AF: 0.148 AC: 313 AN: 2112

Alfa AF: 0.129 Hom.: 6259

Bravo AF: 0.174

Asia WGS AF: 0.101 AC: 352 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.1
DANN	Benign	0.59
PhyloP100		-0.59
Mutation Taster		=99/1	polymorphism

Splicing

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

Other links and lift over

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