1-153373787-A-G

Variant names:

• chr1-153373787-A-G
• rs4772
• NM_005621.2:c.*40T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005621.2. 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
	S100A12	NM_005621.2	MANE Select	c.*40T>C		3_prime_UTR	Exon 3 of 3	NP_005612.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100A12	ENST00000368737.5	TSL:1 MANE Select	c.*40T>C		3_prime_UTR	Exon 3 of 3	ENSP00000357726.3

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

GnomAD2 exomes AF: 0.103 AC: 25701 AN: 249376 AF XY: 0.104

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 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

African (AFR) AF: 0.0933 AC: 3047 AN: 32662

American (AMR) AF: 0.0916 AC: 4053 AN: 44242

Ashkenazi Jewish (ASJ) AF: 0.0944 AC: 2434 AN: 25784

East Asian (EAS) AF: 0.0914 AC: 3609 AN: 39498

South Asian (SAS) AF: 0.105 AC: 8914 AN: 85238

European-Finnish (FIN) AF: 0.0921 AC: 4916 AN: 53366

Middle Eastern (MID) AF: 0.102 AC: 579 AN: 5692

European-Non Finnish (NFE) AF: 0.113 AC: 121480 AN: 1079510

Other (OTH) AF: 0.108 AC: 6371 AN: 59098

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

African (AFR) AF: 0.0920 AC: 3822 AN: 41524

American (AMR) AF: 0.0965 AC: 1477 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0934 AC: 324 AN: 3470

East Asian (EAS) AF: 0.0948 AC: 491 AN: 5178

South Asian (SAS) AF: 0.100 AC: 482 AN: 4818

European-Finnish (FIN) AF: 0.0874 AC: 927 AN: 10602

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.114 AC: 7732 AN: 67992

Other (OTH) AF: 0.109 AC: 229 AN: 2110

Alfa AF: 0.107 Hom.: 1482

Bravo AF: 0.104

Asia WGS AF: 0.0830 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.40
DANN	Benign	0.077
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4772; hg19: chr1-153346263; COSMIC: COSV64199054;