Genetic Variant STIP1:c.673-86C>T (chr11-64197185-C-T) – 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.673-86C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.415 in 1,557,512 control chromosomes in the GnomAD database, including 135,778 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 ( 12234 hom., cov: 31)

Exomes 𝑓: 0.42 ( 123544 hom. )

Consequence

STIP1
NM_006819.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.33

Publications

26 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:

Genome browser will be placed here

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=-0.9).

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
STIP1	NM_006819.3 link	c.673-86C>T	intron_variant	Intron 5 of 13	ENST00000305218.9	NP_006810.1	P31948-1V9HW72
STIP1	NM_001282652.2 link	c.814-86C>T	intron_variant	Intron 5 of 13		NP_001269581.1	P31948-2
STIP1	NM_001282653.2 link	c.601-86C>T	intron_variant	Intron 5 of 13		NP_001269582.1	P31948-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STIP1	ENST00000305218.9 link	c.673-86C>T		intron_variant	Intron 5 of 13	1	NM_006819.3	ENSP00000305958.5		P31948-1

Frequencies

GnomAD3 genomes

AF:

0.396

AC:

60103

AN:

151802

Hom.:

12213

Cov.:

show subpopulations

Gnomad AFR

AF:

0.337

Gnomad AMI

AF:

0.332

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.333

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.401

Gnomad FIN

AF:

0.347

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.421

Gnomad OTH

AF:

0.418

GnomAD4 exome

AF:

0.417

AC:

586167

AN:

1405592

Hom.:

123544

Cov.:

AF XY:

0.415

AC XY:

290120

AN XY:

698300

show subpopulations

African (AFR)

AF:

0.334

AC:

10437

AN:

31210

American (AMR)

AF:

0.562

AC:

21341

AN:

37946

Ashkenazi Jewish (ASJ)

AF:

0.327

AC:

7852

AN:

24042

East Asian (EAS)

AF:

0.352

AC:

13811

AN:

39212

South Asian (SAS)

AF:

0.392

AC:

31570

AN:

80450

European-Finnish (FIN)

AF:

0.356

AC:

18516

AN:

51978

Middle Eastern (MID)

AF:

0.373

AC:

1679

AN:

4500

European-Non Finnish (NFE)

AF:

0.424

AC:

457073

AN:

1078284

Other (OTH)

AF:

0.412

AC:

23888

AN:

57970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

16881

33763

50644

67526

84407

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14098

28196

42294

56392

70490

<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:

0.396

AC:

60167

AN:

151920

Hom.:

12234

Cov.:

AF XY:

0.395

AC XY:

29285

AN XY:

74226

show subpopulations

African (AFR)

AF:

0.337

AC:

13961

AN:

41422

American (AMR)

AF:

0.512

AC:

7812

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.333

AC:

1157

AN:

3472

East Asian (EAS)

AF:

0.335

AC:

1727

AN:

5158

South Asian (SAS)

AF:

0.401

AC:

1938

AN:

4828

European-Finnish (FIN)

AF:

0.347

AC:

3649

AN:

10518

Middle Eastern (MID)

AF:

0.397

AC:

116

AN:

292

European-Non Finnish (NFE)

AF:

0.421

AC:

28614

AN:

67956

Other (OTH)

AF:

0.423

AC:

891

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1831

3662

5493

7324

9155

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

586

1172

1758

2344

2930

<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:

0.412

Hom.:

43821

Bravo

AF:

0.405

Asia WGS

AF:

0.447

AC:

1550

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.24

(source)

DANN

Benign

0.32

PhyloP100

-2.3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over