dbSNP rs3751820: IST1:c.*190A>G (chr16-71928003-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_001270976.1(IST1):c.*190A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.245 in 567,668 control chromosomes in the GnomAD database, including 18,475 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 ( 5030 hom., cov: 32)

Exomes 𝑓: 0.24 ( 13445 hom. )

Consequence

IST1
NM_001270976.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0820

Publications

14 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:

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=-0.83).

BA1

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270976.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IST1	NM_001270975.2	MANE Select	c.*190A>G	3_prime_UTR	Exon 10 of 10	NP_001257904.1
IST1	NM_001270976.1		c.*190A>G	3_prime_UTR	Exon 11 of 11	NP_001257905.1
IST1	NM_014761.4		c.*204A>G	3_prime_UTR	Exon 10 of 10	NP_055576.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
IST1	ENST00000378799.11	TSL:1 MANE Select	c.*190A>G	3_prime_UTR	Exon 10 of 10	ENSP00000368076.6
IST1	ENST00000329908.12	TSL:1	c.*204A>G	3_prime_UTR	Exon 10 of 10	ENSP00000330408.8
IST1	ENST00000378798.9	TSL:1	c.*190A>G	3_prime_UTR	Exon 9 of 9	ENSP00000368075.5

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38175

AN:

152030

Hom.:

5017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.249

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.203

Gnomad ASJ

AF:

0.330

Gnomad EAS

AF:

0.0583

Gnomad SAS

AF:

0.163

Gnomad FIN

AF:

0.255

Gnomad MID

AF:

0.269

Gnomad NFE

AF:

0.279

Gnomad OTH

AF:

0.261

GnomAD4 exome

AF:

0.243

AC:

101025

AN:

415522

Hom.:

13445

Cov.:

AF XY:

0.239

AC XY:

53063

AN XY:

221570

show subpopulations

African (AFR)

AF:

0.257

AC:

2977

AN:

11580

American (AMR)

AF:

0.177

AC:

3136

AN:

17730

Ashkenazi Jewish (ASJ)

AF:

0.323

AC:

3998

AN:

12386

East Asian (EAS)

AF:

0.0490

AC:

1335

AN:

27256

South Asian (SAS)

AF:

0.157

AC:

7072

AN:

45112

European-Finnish (FIN)

AF:

0.238

AC:

6189

AN:

25952

Middle Eastern (MID)

AF:

0.304

AC:

731

AN:

2404

European-Non Finnish (NFE)

AF:

0.279

AC:

69612

AN:

249400

Other (OTH)

AF:

0.252

AC:

5975

AN:

23702

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

3782

7564

11347

15129

18911

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

322

644

966

1288

1610

<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:

0.251

AC:

38220

AN:

152146

Hom.:

5030

Cov.:

AF XY:

0.249

AC XY:

18522

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.250

AC:

10373

AN:

41514

American (AMR)

AF:

0.202

AC:

3091

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.330

AC:

1147

AN:

3472

East Asian (EAS)

AF:

0.0583

AC:

302

AN:

5182

South Asian (SAS)

AF:

0.163

AC:

788

AN:

4826

European-Finnish (FIN)

AF:

0.255

AC:

2701

AN:

10574

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.279

AC:

18975

AN:

67980

Other (OTH)

AF:

0.258

AC:

545

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1469

2937

4406

5874

7343

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:

0.268

Hom.:

23986

Bravo

AF:

0.246

Asia WGS

AF:

0.109

AC:

381

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.28

(source)

DANN

Benign

0.61

PhyloP100

-0.082

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over