rs4980524

chr11-64191787-A-Cchr11-64191787-A-T

Variant summary

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

The NM_006819.3(STIP1):c.10-1291A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 150,618 control chromosomes in the GnomAD database, including 12,110 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 0.40 (12110 hom., cov: 28)
• Consequence: STIP1 NM_006819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STIP1	NM_006819.3	c.10-1291A>C		intron_variant		ENST00000305218.9
STIP1	NM_001282652.2	c.151-1291A>C		intron_variant
STIP1	NM_001282653.2	c.10-1291A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STIP1	ENST00000305218.9	c.10-1291A>C		intron_variant		1	NM_006819.3	P1

Frequencies

GnomAD3 genomes AF: 0.396 AC: 59585 AN: 150502 Hom.: 12090 Cov.: 28

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.335

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.381

Gnomad NFE AF: 0.421

Gnomad OTH AF: 0.418

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

GnomAD4 genome AF: 0.396 AC: 59646 AN: 150618 Hom.: 12110 Cov.: 28 AF XY: 0.395 AC XY: 28987 AN XY: 73454

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.334

Gnomad4 SAS AF: 0.402

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.421

Gnomad4 OTH AF: 0.423

Alfa AF: 0.384 Hom.: 1420

Bravo AF: 0.405

Asia WGS AF: 0.446 AC: 1545 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.6
Dann	Benign	0.53

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: rs4980524; hg19: chr11-63959259;