chr1-153543049-C-G

Variant names:

• chr1-153543049-C-G
• rs743687
• XM_017002029.2:c.22+191G>C

Variant summary

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

The XM_017002029.2(S100A5):​c.22+191G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,100 control chromosomes in the GnomAD database, including 1,619 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 0.12 (1619 hom., cov: 32)
• Consequence: S100A5 XM_017002029.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

Genes affected

S100A5 (HGNC:10495): (S100 calcium binding protein A5) 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 has a Ca2+ affinity 20- to 100-fold higher than the other S100 proteins studied under identical conditions. This protein also binds Zn2+ and Cu2+, and Cu2+ strongly which impairs the binding of Ca2+. This protein is expressed in very restricted regions of the adult brain. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.254 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100A5	XM_017002029.2	c.22+191G>C		intron_variant	Intron 1 of 3		XP_016857518.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17556 AN: 151982 Hom.: 1614 Cov.: 32

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0871

Gnomad ASJ AF: 0.0611

Gnomad EAS AF: 0.0620

Gnomad SAS AF: 0.0790

Gnomad FIN AF: 0.0531

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0556

Gnomad OTH AF: 0.106

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17581 AN: 152100 Hom.: 1619 Cov.: 32 AF XY: 0.114 AC XY: 8479 AN XY: 74360

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.0870

Gnomad4 ASJ AF: 0.0611

Gnomad4 EAS AF: 0.0614

Gnomad4 SAS AF: 0.0792

Gnomad4 FIN AF: 0.0531

Gnomad4 NFE AF: 0.0556

Gnomad4 OTH AF: 0.105

Alfa AF: 0.0802 Hom.: 108

Bravo AF: 0.125

Asia WGS AF: 0.0940 AC: 324 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.61

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs743687; hg19: chr1-153515525;