Genetic Variant NM_001270975.2:c.853-620A>G (chr16-71924149-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001270975.2(IST1):c.853-620A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 455,732 control chromosomes in the GnomAD database, including 14,000 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 0.25 ( 4993 hom., cov: 32)

Exomes 𝑓: 0.23 ( 9007 hom. )

Consequence

IST1
NM_001270975.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.245

Publications

9 publications found

Variant links:

Genes affected

IST1 (HGNC:28977): (IST1 factor associated with ESCRT-III) This gene encodes a protein with MIT-interacting motifs that interacts with components of endosomal sorting complexes required for transport (ESCRT). ESCRT functions in vesicle budding, such as that which occurs during membrane abscission in cytokinesis. There is a pseudogene for this gene on chromosome 19. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Aug 2012]

IST1 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=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
IST1	NM_001270975.2 link	c.853-620A>G		intron_variant	Intron 8 of 9	ENST00000378799.11	NP_001257904.1	P53990-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
IST1	ENST00000378799.11 link	c.853-620A>G		intron_variant	Intron 8 of 9	1	NM_001270975.2	ENSP00000368076.6		P53990-4

Frequencies

GnomAD3 genomes

AF:

0.250

AC:

38006

AN:

151950

Hom.:

4980

Cov.:

show subpopulations

Gnomad AFR

AF:

0.246

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.202

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.0572

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.256

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.263

GnomAD2 exomes

AF:

0.214

AC:

27361

AN:

127982

AF XY:

0.213

show subpopulations

Gnomad AFR exome

AF:

0.256

Gnomad AMR exome

AF:

0.153

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.0517

Gnomad FIN exome

AF:

0.240

Gnomad NFE exome

AF:

0.279

Gnomad OTH exome

AF:

0.246

GnomAD4 exome

AF:

0.231

AC:

70194

AN:

303664

Hom.:

9007

Cov.:

AF XY:

0.225

AC XY:

38975

AN XY:

172936

show subpopulations

African (AFR)

AF:

0.250

AC:

2153

AN:

8606

American (AMR)

AF:

0.152

AC:

4138

AN:

27258

Ashkenazi Jewish (ASJ)

AF:

0.321

AC:

3459

AN:

10782

East Asian (EAS)

AF:

0.0515

AC:

474

AN:

9208

South Asian (SAS)

AF:

0.158

AC:

9427

AN:

59728

European-Finnish (FIN)

AF:

0.241

AC:

2982

AN:

12372

Middle Eastern (MID)

AF:

0.321

AC:

891

AN:

2776

European-Non Finnish (NFE)

AF:

0.272

AC:

43155

AN:

158724

Other (OTH)

AF:

0.247

AC:

3515

AN:

14210

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

2864

5727

8591

11454

14318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

208

416

624

832

1040

<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:

0.250

AC:

38052

AN:

152068

Hom.:

4993

Cov.:

AF XY:

0.248

AC XY:

18439

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.247

AC:

10230

AN:

41478

American (AMR)

AF:

0.202

AC:

3078

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1153

AN:

3472

East Asian (EAS)

AF:

0.0571

AC:

296

AN:

5184

South Asian (SAS)

AF:

0.163

AC:

786

AN:

4820

European-Finnish (FIN)

AF:

0.256

AC:

2701

AN:

10562

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18961

AN:

67984

Other (OTH)

AF:

0.260

AC:

549

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1458

2916

4375

5833

7291

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.265

Hom.:

3519

Bravo

AF:

0.245

Asia WGS

AF:

0.108

AC:

378

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_noAF

Benign

-0.85

CADD

Benign

5.7

(source)

DANN

Benign

0.46

PhyloP100

0.24

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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