Genetic Variant ENST00000358794.9:c.-538C>T (chr11-64185287-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 ENST00000358794.9(STIP1):c.-538C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 162,034 control chromosomes in the GnomAD database, including 1,238 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 0.11 ( 1170 hom., cov: 32)

Exomes 𝑓: 0.10 ( 68 hom. )

Consequence

STIP1
ENST00000358794.9 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.307

Publications

6 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:

ENSG00000288852 (HGNC:):

ENSG00000288852 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=-0.76).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
LOC124902686	XR_007062708.1 link	n.395G>A	non_coding_transcript_exon_variant	Exon 1 of 3
LOC124902686	XR_007062709.1 link	n.395G>A	non_coding_transcript_exon_variant	Exon 1 of 3
LOC124902686	XR_007062710.1 link	n.395G>A	non_coding_transcript_exon_variant	Exon 1 of 4

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
STIP1	ENST00000358794.9 link	c.-538C>T	5_prime_UTR_variant	Exon 1 of 14	1	ENSP00000351646.5	P31948-2
ENSG00000288852	ENST00000686810.2 link	n.430G>A	non_coding_transcript_exon_variant	Exon 1 of 1
ENSG00000288852	ENST00000688681.2 link	n.442G>A	non_coding_transcript_exon_variant	Exon 1 of 1
ENSG00000288852	ENST00000738053.1 link	n.385G>A	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.111

AC:

16867

AN:

152148

Hom.:

1170

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0440

Gnomad AMI

AF:

0.151

Gnomad AMR

AF:

0.0896

Gnomad ASJ

AF:

0.0761

Gnomad EAS

AF:

0.0963

Gnomad SAS

AF:

0.0759

Gnomad FIN

AF:

0.114

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.161

Gnomad OTH

AF:

0.101

GnomAD4 exome

AF:

0.104

AC:

1017

AN:

9770

Hom.:

Cov.:

AF XY:

0.100

AC XY:

527

AN XY:

5258

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.0761

AC:

AN:

1288

Ashkenazi Jewish (ASJ)

AF:

0.0581

AC:

AN:

East Asian (EAS)

AF:

0.0809

AC:

AN:

136

South Asian (SAS)

AF:

0.0590

AC:

115

AN:

1948

European-Finnish (FIN)

AF:

0.0620

AC:

AN:

242

Middle Eastern (MID)

AF:

0.125

AC:

AN:

European-Non Finnish (NFE)

AF:

0.131

AC:

724

AN:

5544

Other (OTH)

AF:

0.102

AC:

AN:

460

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

121

161

201

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.111

AC:

16874

AN:

152264

Hom.:

1170

Cov.:

AF XY:

0.108

AC XY:

8036

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.0441

AC:

1833

AN:

41560

American (AMR)

AF:

0.0896

AC:

1371

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0761

AC:

264

AN:

3468

East Asian (EAS)

AF:

0.0962

AC:

499

AN:

5188

South Asian (SAS)

AF:

0.0764

AC:

368

AN:

4818

European-Finnish (FIN)

AF:

0.114

AC:

1207

AN:

10602

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.161

AC:

10967

AN:

68018

Other (OTH)

AF:

0.0999

AC:

211

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

786

1572

2358

3144

3930

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<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:

0.128

Hom.:

194

Bravo

AF:

0.107

Asia WGS

AF:

0.0850

AC:

296

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.76

CADD

Benign

6.7

(source)

DANN

Benign

0.84

PhyloP100

-0.31

PromoterAI

0.041

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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