rs6591838

Variant names:

• chr11-64191884-A-G
• rs6591838
• NM_006819.3:c.10-1194A>G

Variant summary

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

The NM_006819.3(STIP1):​c.10-1194A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,918 control chromosomes in the GnomAD database, including 4,266 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 (4266 hom., cov: 31)
• Consequence: STIP1 NM_006819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.21
• Publications: 19 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIP1	NM_006819.3	c.10-1194A>G		intron_variant	Intron 1 of 13	ENST00000305218.9	NP_006810.1
STIP1	NM_001282652.2	c.151-1194A>G		intron_variant	Intron 1 of 13		NP_001269581.1
STIP1	NM_001282653.2	c.10-1194A>G		intron_variant	Intron 1 of 13		NP_001269582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIP1	ENST00000305218.9	c.10-1194A>G		intron_variant	Intron 1 of 13	1	NM_006819.3	ENSP00000305958.5

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35412 AN: 151800 Hom.: 4253 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.158

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.233 AC: 35460 AN: 151918 Hom.: 4266 Cov.: 31 AF XY: 0.230 AC XY: 17049 AN XY: 74234

African (AFR) AF: 0.236 AC: 9773 AN: 41448

American (AMR) AF: 0.233 AC: 3553 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.158 AC: 546 AN: 3464

East Asian (EAS) AF: 0.148 AC: 764 AN: 5162

South Asian (SAS) AF: 0.313 AC: 1499 AN: 4788

European-Finnish (FIN) AF: 0.172 AC: 1815 AN: 10574

Middle Eastern (MID) AF: 0.211 AC: 62 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16794 AN: 67926

Other (OTH) AF: 0.223 AC: 471 AN: 2110

Alfa AF: 0.235 Hom.: 550

Bravo AF: 0.235

Asia WGS AF: 0.295 AC: 1024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.20
DANN	Benign	0.18
PhyloP100		-2.2
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

Other links and lift over

dbSNP: rs6591838; hg19: chr11-63959356;