rs6658700

Variant names:

• chr1-45694588-C-T
• rs6658700
• ENST00000359942.8:c.1652-73G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145349.2(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 NM_001145349.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.250
• Publications: 7 publications found

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]

TMEM69 (HGNC:28035): (transmembrane protein 69) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000230896 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145349.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPP	NM_001145349.2		c.1652-73G>A		intron	N/A	NP_001138821.1	Q9Y573-2
	TMEM69	NM_016486.4	MANE Select	c.*683C>T		downstream_gene	N/A	NP_057570.2	Q5SWH9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	IPP	ENST00000359942.8	TSL:1	c.1652-73G>A		intron	N/A	ENSP00000353024.4	Q9Y573-2
	TMEM69	ENST00000372025.5	TSL:1 MANE Select	c.*683C>T		downstream_gene	N/A	ENSP00000361095.4	Q5SWH9
	TMEM69	ENST00000871190.1		c.*683C>T		downstream_gene	N/A	ENSP00000541249.1

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

African (AFR) AF: 0.244 AC: 4174 AN: 17094

American (AMR) AF: 0.325 AC: 10757 AN: 33128

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 5884 AN: 20162

East Asian (EAS) AF: 0.316 AC: 10125 AN: 32046

South Asian (SAS) AF: 0.360 AC: 22732 AN: 63112

European-Finnish (FIN) AF: 0.271 AC: 13080 AN: 48310

Middle Eastern (MID) AF: 0.369 AC: 1570 AN: 4250

European-Non Finnish (NFE) AF: 0.297 AC: 121124 AN: 407612

Other (OTH) AF: 0.300 AC: 10065 AN: 33514

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

African (AFR) AF: 0.241 AC: 9984 AN: 41470

American (AMR) AF: 0.311 AC: 4740 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.285 AC: 989 AN: 3470

East Asian (EAS) AF: 0.346 AC: 1789 AN: 5164

South Asian (SAS) AF: 0.365 AC: 1758 AN: 4816

European-Finnish (FIN) AF: 0.263 AC: 2772 AN: 10540

Middle Eastern (MID) AF: 0.346 AC: 101 AN: 292

European-Non Finnish (NFE) AF: 0.295 AC: 20023 AN: 67970

Other (OTH) AF: 0.310 AC: 655 AN: 2114

Alfa AF: 0.283 Hom.: 1040

Bravo AF: 0.284

Asia WGS AF: 0.346 AC: 1205 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	7.2
DANN	Benign	0.56
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs6658700;

hg19: chr1-46160260;

COSMIC: COSV63433594;