rs2845597

Positions:

• chr11-64186898-G-A

Variant summary

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

The NM_006819.3(STIP1):​c.9+628G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 152,048 control chromosomes in the GnomAD database, including 8,626 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 0.33 (8626 hom., cov: 31)
• Consequence: STIP1 NM_006819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.89

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]

STIP1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIP1	NM_006819.3	c.9+628G>A		intron_variant		ENST00000305218.9	NP_006810.1
STIP1	NM_001282652.2	c.150+924G>A		intron_variant			NP_001269581.1
STIP1	NM_001282653.2	c.9+628G>A		intron_variant			NP_001269582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIP1	ENST00000305218.9	c.9+628G>A		intron_variant		1	NM_006819.3	ENSP00000305958.5

Frequencies

GnomAD3 genomes AF: 0.333 AC: 50648 AN: 151928 Hom.: 8611 Cov.: 31

Gnomad AFR AF: 0.308

Gnomad AMI AF: 0.293

Gnomad AMR AF: 0.398

Gnomad ASJ AF: 0.263

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.295

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.352

Gnomad OTH AF: 0.335

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

GnomAD4 genome AF: 0.333 AC: 50699 AN: 152048 Hom.: 8626 Cov.: 31 AF XY: 0.331 AC XY: 24627 AN XY: 74314

Gnomad4 AFR AF: 0.308

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.263

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.279

Gnomad4 FIN AF: 0.295

Gnomad4 NFE AF: 0.352

Gnomad4 OTH AF: 0.339

Alfa AF: 0.337 Hom.: 2095

Bravo AF: 0.340

Asia WGS AF: 0.339 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2845597; hg19: chr11-63954370;