rs7197486

Positions:

• chr16-71924149-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
IST1	NM_001270975.2	c.853-620A>G		intron_variant		ENST00000378799.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IST1	ENST00000378799.11	c.853-620A>G		intron_variant		1	NM_001270975.2	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38006 AN: 151950 Hom.: 4980 Cov.: 32

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

GnomAD3 exomes AF: 0.214 AC: 27361 AN: 127982 Hom.: 3408 AF XY: 0.213 AC XY: 14964 AN XY: 70096

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 SAS exome AF: 0.155

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.: 0 AF XY: 0.225 AC XY: 38975 AN XY: 172936

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.152

Gnomad4 ASJ exome AF: 0.321

Gnomad4 EAS exome AF: 0.0515

Gnomad4 SAS exome AF: 0.158

Gnomad4 FIN exome AF: 0.241

Gnomad4 NFE exome AF: 0.272

Gnomad4 OTH exome AF: 0.247

GnomAD4 genome AF: 0.250 AC: 38052 AN: 152068 Hom.: 4993 Cov.: 32 AF XY: 0.248 AC XY: 18439 AN XY: 74334

Gnomad4 AFR AF: 0.247

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.0571

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.256

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.260

Alfa AF: 0.263 Hom.: 3179

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
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
DANN	Benign	0.46
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs7197486; hg19: chr16-71958052;