chr1-153373787-A-G

Position:

• chr1-153373787-A-G

Variant summary

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

The NM_005621.2(S100A12):​c.*40T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,577,288 control chromosomes in the GnomAD database, including 9,497 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 0.10 (789 hom., cov: 32)
  • Exomes 𝑓: 0.11 (8708 hom.)
• Consequence: S100A12 NM_005621.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72

Genes affected

S100A12 (HGNC:10489): (S100 calcium binding protein A12) 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 is proposed to be involved in specific calcium-dependent signal transduction pathways and its regulatory effect on cytoskeletal components may modulate various neutrophil activities. The protein includes an antimicrobial peptide which has antibacterial activity. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
S100A12	NM_005621.2	c.*40T>C		3_prime_UTR_variant	3/3	ENST00000368737.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
S100A12	ENST00000368737.5	c.*40T>C		3_prime_UTR_variant	3/3	1	NM_005621.2	P1

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15608 AN: 152080 Hom.: 788 Cov.: 32

Gnomad AFR AF: 0.0921

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0965

Gnomad ASJ AF: 0.0934

Gnomad EAS AF: 0.0952

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0874

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.105

GnomAD3 exomes AF: 0.103 AC: 25701 AN: 249376 Hom.: 1354 AF XY: 0.104 AC XY: 14005 AN XY: 134906

Gnomad AFR exome AF: 0.0946

Gnomad AMR exome AF: 0.0897

Gnomad ASJ exome AF: 0.0987

Gnomad EAS exome AF: 0.0937

Gnomad SAS exome AF: 0.105

Gnomad FIN exome AF: 0.0930

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.113

GnomAD4 exome AF: 0.109 AC: 155403 AN: 1425090 Hom.: 8708 Cov.: 26 AF XY: 0.109 AC XY: 77711 AN XY: 710862

Gnomad4 AFR exome AF: 0.0933

Gnomad4 AMR exome AF: 0.0916

Gnomad4 ASJ exome AF: 0.0944

Gnomad4 EAS exome AF: 0.0914

Gnomad4 SAS exome AF: 0.105

Gnomad4 FIN exome AF: 0.0921

Gnomad4 NFE exome AF: 0.113

Gnomad4 OTH exome AF: 0.108

GnomAD4 genome AF: 0.103 AC: 15616 AN: 152198 Hom.: 789 Cov.: 32 AF XY: 0.102 AC XY: 7584 AN XY: 74410

Gnomad4 AFR AF: 0.0920

Gnomad4 AMR AF: 0.0965

Gnomad4 ASJ AF: 0.0934

Gnomad4 EAS AF: 0.0948

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0874

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.109

Alfa AF: 0.106 Hom.: 1020

Bravo AF: 0.104

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.40
DANN	Benign	0.077

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4772; hg19: chr1-153346263; COSMIC: COSV64199054;