rs6658700

chr1-45694588-C-T

Variant summary

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

The ENST00000359942.8(IPP):c.1652-73G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 811,234 control chromosomes in the GnomAD database, including 36,995 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 0.28 (6236 hom., cov: 32)
  • Exomes 𝑓: 0.30 (30759 hom.)
• Consequence: IPP ENST00000359942.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250

Genes affected

IPP (HGNC:6108): (intracisternal A particle-promoted polypeptide) The protein encoded by this gene is a member of the kelch family of proteins, which is characterized by a 50 amino acid repeat which interacts with actin. Transcript variants have been described but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
IPP	NM_001145349.2	c.1652-73G>A		intron_variant
IPP	XM_047419673.1	c.1652-73G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
IPP	ENST00000359942.8	c.1652-73G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.283 AC: 43032 AN: 151888 Hom.: 6216 Cov.: 32

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.310

Gnomad ASJ AF: 0.285

Gnomad EAS AF: 0.346

Gnomad SAS AF: 0.365

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.341

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.302

GnomAD4 exome AF: 0.303 AC: 199511 AN: 659228 Hom.: 30759 Cov.: 9 AF XY: 0.305 AC XY: 106834 AN XY: 349810

Gnomad4 AFR exome AF: 0.244

Gnomad4 AMR exome AF: 0.325

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.316

Gnomad4 SAS exome AF: 0.360

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.297

Gnomad4 OTH exome AF: 0.300

GnomAD4 genome AF: 0.283 AC: 43091 AN: 152006 Hom.: 6236 Cov.: 32 AF XY: 0.284 AC XY: 21086 AN XY: 74274

Gnomad4 AFR AF: 0.241

Gnomad4 AMR AF: 0.311

Gnomad4 ASJ AF: 0.285

Gnomad4 EAS AF: 0.346

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.263

Gnomad4 NFE AF: 0.295

Gnomad4 OTH AF: 0.310

Alfa AF: 0.285 Hom.: 1022

Bravo AF: 0.284

Asia WGS AF: 0.346 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
Cadd	Benign	7.2
Dann	Benign	0.56

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6658700; hg19: chr1-46160260; COSMIC: COSV63433594;