rs3751820

Positions:

• chr16-71928003-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.*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_001270975.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
IST1	NM_001270975.2	c.*190A>G		3_prime_UTR_variant	10/10	ENST00000378799.11	NP_001257904.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
IST1	ENST00000378799.11	c.*190A>G		3_prime_UTR_variant	10/10	1	NM_001270975.2	ENSP00000368076.6

Frequencies

GnomAD3 genomes AF: 0.251 AC: 38175 AN: 152030 Hom.: 5017 Cov.: 32

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.: 4 AF XY: 0.239 AC XY: 53063 AN XY: 221570

Gnomad4 AFR exome AF: 0.257

Gnomad4 AMR exome AF: 0.177

Gnomad4 ASJ exome AF: 0.323

Gnomad4 EAS exome AF: 0.0490

Gnomad4 SAS exome AF: 0.157

Gnomad4 FIN exome AF: 0.238

Gnomad4 NFE exome AF: 0.279

Gnomad4 OTH exome AF: 0.252

GnomAD4 genome AF: 0.251 AC: 38220 AN: 152146 Hom.: 5030 Cov.: 32 AF XY: 0.249 AC XY: 18522 AN XY: 74376

Gnomad4 AFR AF: 0.250

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.0583

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.279

Gnomad4 OTH AF: 0.258

Alfa AF: 0.273 Hom.: 11635

Bravo AF: 0.246

Asia WGS AF: 0.109 AC: 381 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.28
DANN	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3751820; hg19: chr16-71961906;