NM_006819.3:c.9+628G>A

Variant names:

• chr11-64186898-G-A
• rs2845597
• NM_006819.3:c.9+628G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006819.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIP1	NM_006819.3	MANE Select	c.9+628G>A		intron	N/A	NP_006810.1
	STIP1	NM_001282652.2		c.150+924G>A		intron	N/A	NP_001269581.1
	STIP1	NM_001282653.2		c.9+628G>A		intron	N/A	NP_001269582.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STIP1	ENST00000305218.9	TSL:1 MANE Select	c.9+628G>A		intron	N/A	ENSP00000305958.5
	STIP1	ENST00000358794.9	TSL:1	c.150+924G>A		intron	N/A	ENSP00000351646.5
	STIP1	ENST00000543847.1	TSL:1	c.9+628G>A		intron	N/A	ENSP00000442704.1

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

African (AFR) AF: 0.308 AC: 12753 AN: 41460

American (AMR) AF: 0.398 AC: 6080 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.263 AC: 910 AN: 3466

East Asian (EAS) AF: 0.293 AC: 1516 AN: 5168

South Asian (SAS) AF: 0.279 AC: 1345 AN: 4826

European-Finnish (FIN) AF: 0.295 AC: 3122 AN: 10572

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.352 AC: 23916 AN: 67966

Other (OTH) AF: 0.339 AC: 717 AN: 2112

Alfa AF: 0.336 Hom.: 2129

Bravo AF: 0.340

Asia WGS AF: 0.339 AC: 1174 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.14
DANN	Benign	0.78
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2845597; hg19: chr11-63954370;