rs12132927

Variant names:

• chr1-153459085-T-C
• rs12132927
• NM_002963.4:c.-17-55A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A7	NM_002963.4	MANE Select	c.-17-55A>G		intron	N/A	NP_002954.2	P31151

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A7	ENST00000368723.4	TSL:1 MANE Select	c.-17-55A>G		intron	N/A	ENSP00000357712.3	P31151
	S100A7	ENST00000948759.1		c.-72A>G		5_prime_UTR	Exon 1 of 2	ENSP00000618818.1
	S100A7	ENST00000368722.5	TSL:3	c.-17-55A>G		intron	N/A	ENSP00000357711.1	P31151

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

African (AFR) AF: 0.0143 AC: 467 AN: 32572

American (AMR) AF: 0.0407 AC: 1706 AN: 41896

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3627 AN: 24168

East Asian (EAS) AF: 0.000228 AC: 9 AN: 39436

South Asian (SAS) AF: 0.0895 AC: 7253 AN: 81062

European-Finnish (FIN) AF: 0.0665 AC: 3445 AN: 51770

Middle Eastern (MID) AF: 0.122 AC: 685 AN: 5606

European-Non Finnish (NFE) AF: 0.0917 AC: 100364 AN: 1094586

Other (OTH) AF: 0.0854 AC: 5044 AN: 59064

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

African (AFR) AF: 0.0158 AC: 655 AN: 41552

American (AMR) AF: 0.0584 AC: 893 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 560 AN: 3466

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5184

South Asian (SAS) AF: 0.0825 AC: 397 AN: 4814

European-Finnish (FIN) AF: 0.0647 AC: 686 AN: 10602

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0915 AC: 6224 AN: 67996

Other (OTH) AF: 0.0821 AC: 173 AN: 2108

Alfa AF: 0.0850 Hom.: 1029

Bravo AF: 0.0594

Asia WGS AF: 0.0350 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.83
DANN	Benign	0.66
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12132927; hg19: chr1-153431561;