rs12132927

Positions:

• chr1-153459085-T-C

Variant summary

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

The NM_002963.4(S100A7):​c.-17-55A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0836 in 1,582,376 control chromosomes in the GnomAD database, including 6,119 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 0.063 (426 hom., cov: 32)
  • Exomes 𝑓: 0.086 (5693 hom.)
• Consequence: S100A7 NM_002963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84

Genes affected

S100A7 (HGNC:10497): (S100 calcium binding protein A7) 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 differs from the other S100 proteins of known structure in its lack of calcium binding ability in one EF-hand at the N-terminus. The protein is overexpressed in hyperproliferative skin diseases, exhibits antimicrobial activities against bacteria and induces immunomodulatory activities. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
S100A7	NM_002963.4	c.-17-55A>G		intron_variant		ENST00000368723.4	NP_002954.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
S100A7	ENST00000368723.4	c.-17-55A>G		intron_variant		1	NM_002963.4	ENSP00000357712.3
S100A7	ENST00000368722.5	c.-17-55A>G		intron_variant		3		ENSP00000357711.1

Frequencies

GnomAD3 genomes AF: 0.0635 AC: 9654 AN: 152098 Hom.: 426 Cov.: 32

Gnomad AFR AF: 0.0158

Gnomad AMI AF: 0.0396

Gnomad AMR AF: 0.0585

Gnomad ASJ AF: 0.162

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.0818

Gnomad FIN AF: 0.0647

Gnomad MID AF: 0.104

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.0825

GnomAD4 exome AF: 0.0857 AC: 122600 AN: 1430160 Hom.: 5693 AF XY: 0.0869 AC XY: 61567 AN XY: 708514

Gnomad4 AFR exome AF: 0.0143

Gnomad4 AMR exome AF: 0.0407

Gnomad4 ASJ exome AF: 0.150

Gnomad4 EAS exome AF: 0.000228

Gnomad4 SAS exome AF: 0.0895

Gnomad4 FIN exome AF: 0.0665

Gnomad4 NFE exome AF: 0.0917

Gnomad4 OTH exome AF: 0.0854

GnomAD4 genome AF: 0.0635 AC: 9659 AN: 152216 Hom.: 426 Cov.: 32 AF XY: 0.0621 AC XY: 4623 AN XY: 74426

Gnomad4 AFR AF: 0.0158

Gnomad4 AMR AF: 0.0584

Gnomad4 ASJ AF: 0.162

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0825

Gnomad4 FIN AF: 0.0647

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.0821

Alfa AF: 0.0871 Hom.: 854

Bravo AF: 0.0594

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.66

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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

Other links and lift over

dbSNP: rs12132927; hg19: chr1-153431561;