4-6696039-T-G

Variant names:

• chr4-6696039-T-G
• rs3822262
• NM_005980.3:c.139-854T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005980.3(S100P):​c.139-854T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.264 in 152,188 control chromosomes in the GnomAD database, including 5,822 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 0.26 (5822 hom., cov: 34)
• Consequence: S100P NM_005980.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 36 publications found

Genes affected

S100P (HGNC:10504): (S100 calcium binding protein P) 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; however, this gene is located at 4p16. This protein, in addition to binding Ca2+, also binds Zn2+ and Mg2+. This protein may play a role in the etiology of prostate cancer. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.636 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005980.3. 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
	S100P	NM_005980.3	MANE Select	c.139-854T>G		intron	N/A	NP_005971.1	P25815

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	S100P	ENST00000296370.4	TSL:1 MANE Select	c.139-854T>G		intron	N/A	ENSP00000296370.3	P25815
	S100P	ENST00000513778.1	TSL:3	n.36-854T>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.263 AC: 40062 AN: 152070 Hom.: 5810 Cov.: 34

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.299

Gnomad ASJ AF: 0.220

Gnomad EAS AF: 0.655

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.196

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.264 AC: 40109 AN: 152188 Hom.: 5822 Cov.: 34 AF XY: 0.264 AC XY: 19669 AN XY: 74396

African (AFR) AF: 0.259 AC: 10755 AN: 41510

American (AMR) AF: 0.299 AC: 4573 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.220 AC: 763 AN: 3470

East Asian (EAS) AF: 0.655 AC: 3378 AN: 5160

South Asian (SAS) AF: 0.345 AC: 1668 AN: 4828

European-Finnish (FIN) AF: 0.196 AC: 2077 AN: 10624

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.236 AC: 16034 AN: 68000

Other (OTH) AF: 0.274 AC: 579 AN: 2110

Alfa AF: 0.251 Hom.: 22843

Bravo AF: 0.270

Asia WGS AF: 0.483 AC: 1676 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.23
DANN	Benign	0.55
PhyloP100		-2.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3822262;

hg19: chr4-6697766;