dbSNP rs2282490: STIP1:c.503+60T>C (chr11-64194680-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006819.3(STIP1):c.503+60T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,584,280 control chromosomes in the GnomAD database, including 24,047 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 0.16 ( 2245 hom., cov: 32)

Exomes 𝑓: 0.17 ( 21802 hom. )

Consequence

STIP1
NM_006819.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.353

Publications

20 publications found

Variant links:

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]

STIP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STIP1	NM_006819.3	MANE Select	c.503+60T>C	intron	N/A	NP_006810.1
STIP1	NM_001282652.2		c.644+60T>C	intron	N/A	NP_001269581.1
STIP1	NM_001282653.2		c.431+60T>C	intron	N/A	NP_001269582.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STIP1	ENST00000305218.9	TSL:1 MANE Select	c.503+60T>C	intron	N/A	ENSP00000305958.5
STIP1	ENST00000358794.9	TSL:1	c.644+60T>C	intron	N/A	ENSP00000351646.5
STIP1	ENST00000543847.1	TSL:1	c.503+60T>C	intron	N/A	ENSP00000442704.1

Frequencies

GnomAD3 genomes

AF:

0.163

AC:

24752

AN:

151994

Hom.:

2241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.129

Gnomad AMR

AF:

0.279

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.185

Gnomad SAS

AF:

0.0884

Gnomad FIN

AF:

0.173

Gnomad MID

AF:

0.172

Gnomad NFE

AF:

0.173

Gnomad OTH

AF:

0.194

GnomAD4 exome

AF:

0.170

AC:

244173

AN:

1432168

Hom.:

21802

AF XY:

0.168

AC XY:

119517

AN XY:

709348

show subpopulations

African (AFR)

AF:

0.0995

AC:

3259

AN:

32768

American (AMR)

AF:

0.306

AC:

12730

AN:

41564

Ashkenazi Jewish (ASJ)

AF:

0.177

AC:

4391

AN:

24786

East Asian (EAS)

AF:

0.184

AC:

7158

AN:

38932

South Asian (SAS)

AF:

0.0964

AC:

7980

AN:

82788

European-Finnish (FIN)

AF:

0.170

AC:

8885

AN:

52300

Middle Eastern (MID)

AF:

0.189

AC:

1072

AN:

5674

European-Non Finnish (NFE)

AF:

0.172

AC:

188059

AN:

1094162

Other (OTH)

AF:

0.180

AC:

10639

AN:

59194

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

10304

20609

30913

41218

51522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6726

13452

20178

26904

33630

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.163

AC:

24768

AN:

152112

Hom.:

2245

Cov.:

AF XY:

0.165

AC XY:

12265

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.104

AC:

4334

AN:

41528

American (AMR)

AF:

0.279

AC:

4261

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

610

AN:

3472

East Asian (EAS)

AF:

0.185

AC:

954

AN:

5168

South Asian (SAS)

AF:

0.0886

AC:

428

AN:

4828

European-Finnish (FIN)

AF:

0.173

AC:

1835

AN:

10586

Middle Eastern (MID)

AF:

0.178

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.173

AC:

11756

AN:

67954

Other (OTH)

AF:

0.200

AC:

421

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1073

2146

3220

4293

5366

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

260

520

780

1040

1300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.173

Hom.:

4434

Bravo

AF:

0.171

Asia WGS

AF:

0.152

AC:

525

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

3.1

(source)

DANN

Benign

0.47

PhyloP100

0.35

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over