dbSNP rs2236647: STIP1:c.673-138C>T (chr11-64197133-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.673-138C>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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.33

Publications

28 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=-0.98).

BA1

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

Transcripts

RefSeq

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

show subpopulations

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.:

AF XY:

0.452

AC XY:

215146

AN XY:

475752

show subpopulations

African (AFR)

AF:

0.728

AC:

15639

AN:

21490

American (AMR)

AF:

0.585

AC:

13310

AN:

22762

Ashkenazi Jewish (ASJ)

AF:

0.400

AC:

6977

AN:

17432

East Asian (EAS)

AF:

0.420

AC:

14599

AN:

34758

South Asian (SAS)

AF:

0.556

AC:

31653

AN:

56966

European-Finnish (FIN)

AF:

0.360

AC:

16700

AN:

46432

Middle Eastern (MID)

AF:

0.459

AC:

1368

AN:

2978

European-Non Finnish (NFE)

AF:

0.437

AC:

306312

AN:

700586

Other (OTH)

AF:

0.469

AC:

19789

AN:

42210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11540

23080

34621

46161

57701

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8244

16488

24732

32976

41220

<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:

0.523

AC:

79407

AN:

151898

Hom.:

22188

Cov.:

AF XY:

0.520

AC XY:

38606

AN XY:

74252

show subpopulations

African (AFR)

AF:

0.720

AC:

29847

AN:

41444

American (AMR)

AF:

0.569

AC:

8674

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.406

AC:

1409

AN:

3470

East Asian (EAS)

AF:

0.397

AC:

2049

AN:

5164

South Asian (SAS)

AF:

0.572

AC:

2757

AN:

4820

European-Finnish (FIN)

AF:

0.348

AC:

3664

AN:

10524

Middle Eastern (MID)

AF:

0.514

AC:

150

AN:

292

European-Non Finnish (NFE)

AF:

0.433

AC:

29434

AN:

67932

Other (OTH)

AF:

0.521

AC:

1098

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1783

3566

5349

7132

8915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.514

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

(source)

DANN

Benign

0.57

PhyloP100

-1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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