16-71924149-A-G

Variant names:

• chr16-71924149-A-G
• rs7197486
• NM_001270975.2:c.853-620A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001270975.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IST1	NM_001270975.2	MANE Select	c.853-620A>G		intron	N/A	NP_001257904.1
	IST1	NM_001270976.1		c.892-620A>G		intron	N/A	NP_001257905.1
	IST1	NM_014761.4		c.853-624A>G		intron	N/A	NP_055576.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IST1	ENST00000378799.11	TSL:1 MANE Select	c.853-620A>G		intron	N/A	ENSP00000368076.6
	IST1	ENST00000329908.12	TSL:1	c.853-624A>G		intron	N/A	ENSP00000330408.8
	IST1	ENST00000378798.9	TSL:1	c.760-620A>G		intron	N/A	ENSP00000368075.5

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

GnomAD2 exomes AF: 0.214 AC: 27361 AN: 127982 AF XY: 0.213

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

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

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

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: 78 AN: 294

European-Non Finnish (NFE) AF: 0.279 AC: 18961 AN: 67984

Other (OTH) AF: 0.260 AC: 549 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.7
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)

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

Other links and lift over

dbSNP: rs7197486; hg19: chr16-71958052;