rs4980524

Variant names:

• chr11-64191787-A-C
• rs4980524
• NM_006819.3:c.10-1291A>C

Your query was ambiguous. Multiple possible variants found:

• chr11-64191787-A-C
• chr11-64191787-A-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.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
• Publications: 15 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=-0.77).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.503 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.10-1291A>C		intron	N/A	NP_006810.1
	STIP1	NM_001282652.2		c.151-1291A>C		intron	N/A	NP_001269581.1
	STIP1	NM_001282653.2		c.10-1291A>C		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.10-1291A>C		intron	N/A	ENSP00000305958.5
	STIP1	ENST00000358794.9	TSL:1	c.151-1291A>C		intron	N/A	ENSP00000351646.5
	STIP1	ENST00000543847.1	TSL:1	c.10-1291A>C		intron	N/A	ENSP00000442704.1

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

African (AFR) AF: 0.337 AC: 13777 AN: 40912

American (AMR) AF: 0.512 AC: 7741 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1155 AN: 3462

East Asian (EAS) AF: 0.334 AC: 1705 AN: 5102

South Asian (SAS) AF: 0.402 AC: 1916 AN: 4768

European-Finnish (FIN) AF: 0.347 AC: 3563 AN: 10282

Middle Eastern (MID) AF: 0.390 AC: 113 AN: 290

European-Non Finnish (NFE) AF: 0.421 AC: 28490 AN: 67694

Other (OTH) AF: 0.423 AC: 886 AN: 2094

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	1.6
DANN	Benign	0.53
PhyloP100		-1.0
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: rs4980524; hg19: chr11-63959259;