rs7941773

Positions:

• chr11-64185287-C-T

Variant summary

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

The NM_001282652.2(STIP1):​c.-538C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 162,034 control chromosomes in the GnomAD database, including 1,238 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 0.11 (1170 hom., cov: 32)
  • Exomes 𝑓: 0.10 (68 hom.)
• Consequence: STIP1 NM_001282652.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.307

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]

ENSG00000289486 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STIP1	NM_001282652.2	c.-538C>T		5_prime_UTR_variant	1/14		NP_001269581.1
LOC124902686	XR_007062708.1	n.395G>A		non_coding_transcript_exon_variant	1/3
LOC124902686	XR_007062709.1	n.395G>A		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STIP1	ENST00000358794	c.-538C>T		5_prime_UTR_variant	1/14	1		ENSP00000351646.5
ENSG00000289486	ENST00000686810.2	n.430G>A		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16867 AN: 152148 Hom.: 1170 Cov.: 32

Gnomad AFR AF: 0.0440

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0896

Gnomad ASJ AF: 0.0761

Gnomad EAS AF: 0.0963

Gnomad SAS AF: 0.0759

Gnomad FIN AF: 0.114

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.104 AC: 1017 AN: 9770 Hom.: 68 Cov.: 0 AF XY: 0.100 AC XY: 527 AN XY: 5258

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0761

Gnomad4 ASJ exome AF: 0.0581

Gnomad4 EAS exome AF: 0.0809

Gnomad4 SAS exome AF: 0.0590

Gnomad4 FIN exome AF: 0.0620

Gnomad4 NFE exome AF: 0.131

Gnomad4 OTH exome AF: 0.102

GnomAD4 genome AF: 0.111 AC: 16874 AN: 152264 Hom.: 1170 Cov.: 32 AF XY: 0.108 AC XY: 8036 AN XY: 74454

Gnomad4 AFR AF: 0.0441

Gnomad4 AMR AF: 0.0896

Gnomad4 ASJ AF: 0.0761

Gnomad4 EAS AF: 0.0962

Gnomad4 SAS AF: 0.0764

Gnomad4 FIN AF: 0.114

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.0999

Alfa AF: 0.131 Hom.: 192

Bravo AF: 0.107

Asia WGS AF: 0.0850 AC: 296 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	6.7
DANN	Benign	0.84

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7941773; hg19: chr11-63952759;