rs2236647

Variant names:

• chr11-64197133-C-T
• rs2236647
• NM_006819.3:c.673-138C>T

Variant summary

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

The NM_006819.3(STIP1):​c.673-138C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.461 in 1,097,512 control chromosomes in the GnomAD database, including 120,404 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 0.52 (22188 hom., cov: 31)
  • Exomes 𝑓: 0.45 (98216 hom.)
• Consequence: STIP1 NM_006819.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.33

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STIP1	NM_006819.3	c.673-138C>T		intron_variant	Intron 5 of 13	ENST00000305218.9	NP_006810.1
STIP1	NM_001282652.2	c.814-138C>T		intron_variant	Intron 5 of 13		NP_001269581.1
STIP1	NM_001282653.2	c.601-138C>T		intron_variant	Intron 5 of 13		NP_001269582.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIP1	ENST00000305218.9	c.673-138C>T		intron_variant	Intron 5 of 13	1	NM_006819.3	ENSP00000305958.5

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79318 AN: 151780 Hom.: 22149 Cov.: 31

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.406

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.573

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.517

GnomAD4 exome AF: 0.451 AC: 426347 AN: 945614 Hom.: 98216 Cov.: 12 AF XY: 0.452 AC XY: 215146 AN XY: 475752

Gnomad4 AFR exome AF: 0.728 AC: 15639 AN: 21490

Gnomad4 AMR exome AF: 0.585 AC: 13310 AN: 22762

Gnomad4 ASJ exome AF: 0.400 AC: 6977 AN: 17432

Gnomad4 EAS exome AF: 0.420 AC: 14599 AN: 34758

Gnomad4 SAS exome AF: 0.556 AC: 31653 AN: 56966

Gnomad4 FIN exome AF: 0.360 AC: 16700 AN: 46432

Gnomad4 NFE exome AF: 0.437 AC: 306312 AN: 700586

Gnomad4 Remaining exome AF: 0.469 AC: 19789 AN: 42210

GnomAD4 genome AF: 0.523 AC: 79407 AN: 151898 Hom.: 22188 Cov.: 31 AF XY: 0.520 AC XY: 38606 AN XY: 74252

Gnomad4 AFR AF: 0.720 AC: 0.720177 AN: 0.720177

Gnomad4 AMR AF: 0.569 AC: 0.569384 AN: 0.569384

Gnomad4 ASJ AF: 0.406 AC: 0.406052 AN: 0.406052

Gnomad4 EAS AF: 0.397 AC: 0.396785 AN: 0.396785

Gnomad4 SAS AF: 0.572 AC: 0.571992 AN: 0.571992

Gnomad4 FIN AF: 0.348 AC: 0.348157 AN: 0.348157

Gnomad4 NFE AF: 0.433 AC: 0.433286 AN: 0.433286

Gnomad4 OTH AF: 0.521 AC: 0.521368 AN: 0.521368

Alfa AF: 0.514 Hom.: 6971

Bravo AF: 0.543

Asia WGS AF: 0.571 AC: 1981 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.4
DANN	Benign	0.57
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

Publications

LitVar

Other links and lift over

dbSNP: rs2236647; hg19: chr11-63964605;