chr5-76928346-G-C

Variant names:

• chr5-76928346-G-C
• rs2460504
• NM_001437779.1:c.*3-6342G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001437779.1(S100Z):​c.*3-6342G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 152,108 control chromosomes in the GnomAD database, including 4,136 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 0.23 (4136 hom., cov: 34)
• Consequence: S100Z NM_001437779.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.530
• Publications: 4 publications found

Genes affected

S100Z (HGNC:30367): (S100 calcium binding protein Z) Members of the S100 protein family contain 2 calcium-binding EF-hands and exhibit cell-type specific expression patterns. For additional background information on S100 proteins, see MIM 114085.[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
S100Z	NM_001437779.1	c.*3-6342G>C		intron_variant	Intron 4 of 4		NP_001424708.1
S100Z	NM_001437783.1	c.*3-6342G>C		intron_variant	Intron 2 of 2		NP_001424712.1
S100Z	XM_011543241.3	c.*3-24489G>C		intron_variant	Intron 4 of 4		XP_011541543.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.225 AC: 34264 AN: 151990 Hom.: 4131 Cov.: 34

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.225 AC: 34281 AN: 152108 Hom.: 4136 Cov.: 34 AF XY: 0.229 AC XY: 17041 AN XY: 74332

African (AFR) AF: 0.169 AC: 7001 AN: 41498

American (AMR) AF: 0.210 AC: 3201 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 762 AN: 3470

East Asian (EAS) AF: 0.357 AC: 1844 AN: 5160

South Asian (SAS) AF: 0.189 AC: 911 AN: 4818

European-Finnish (FIN) AF: 0.335 AC: 3547 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16190 AN: 67992

Other (OTH) AF: 0.230 AC: 486 AN: 2114

Alfa AF: 0.130 Hom.: 251

Bravo AF: 0.215

Asia WGS AF: 0.305 AC: 1060 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	9.7
DANN	Benign	0.80
PhyloP100		0.53

Splicing

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

Other links and lift over

dbSNP: rs2460504; hg19: chr5-76224171;