rs2282490

Positions:

• chr11-64194680-T-C

Variant summary

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

The NM_006819.3(STIP1):​c.503+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,584,280 control chromosomes in the GnomAD database, including 24,047 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 0.16 (2245 hom., cov: 32)
  • Exomes 𝑓: 0.17 (21802 hom.)
• Consequence: STIP1 NM_006819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

Genes affected

STIP1 (HGNC:11387): (stress induced phosphoprotein 1) STIP1 is an adaptor protein that coordinates the functions of HSP70 (see HSPA1A; MIM 140550) and HSP90 (see HSP90AA1; MIM 140571) in protein folding. It is thought to assist in the transfer of proteins from HSP70 to HSP90 by binding both HSP90 and substrate-bound HSP70. STIP1 also stimulates the ATPase activity of HSP70 and inhibits the ATPase activity of HSP90, suggesting that it regulates both the conformations and ATPase cycles of these chaperones (Song and Masison, 2005 [PubMed 16100115]).[supplied by OMIM, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIP1	NM_006819.3	c.503+60T>C		intron_variant		ENST00000305218.9
STIP1	NM_001282652.2	c.644+60T>C		intron_variant
STIP1	NM_001282653.2	c.431+60T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIP1	ENST00000305218.9	c.503+60T>C		intron_variant		1	NM_006819.3	P1

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24752 AN: 151994 Hom.: 2241 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.185

Gnomad SAS AF: 0.0884

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.172

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.194

GnomAD4 exome AF: 0.170 AC: 244173 AN: 1432168 Hom.: 21802 AF XY: 0.168 AC XY: 119517 AN XY: 709348

Gnomad4 AFR exome AF: 0.0995

Gnomad4 AMR exome AF: 0.306

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.184

Gnomad4 SAS exome AF: 0.0964

Gnomad4 FIN exome AF: 0.170

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.180

GnomAD4 genome AF: 0.163 AC: 24768 AN: 152112 Hom.: 2245 Cov.: 32 AF XY: 0.165 AC XY: 12265 AN XY: 74370

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.185

Gnomad4 SAS AF: 0.0886

Gnomad4 FIN AF: 0.173

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.200

Alfa AF: 0.173 Hom.: 3079

Bravo AF: 0.171

Asia WGS AF: 0.152 AC: 525 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.47

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: rs2282490; hg19: chr11-63962152; COSMIC: COSV59441423; COSMIC: COSV59441423;