dbSNP rs6658700: IPP:c.1652-73G>A (chr1-45694588-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.250

Publications

7 publications found

Variant links:

COSMIC-nc: COSV63433594

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]

IPP links:

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

TMEM69 links:

ENSG00000230896 (HGNC:):

ENSG00000230896 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
IPP	NM_001145349.2 link	c.1652-73G>A	intron_variant	Intron 9 of 9		NP_001138821.1	Q9Y573-2
IPP	XM_047419673.1 link	c.1652-73G>A	intron_variant	Intron 9 of 9		XP_047275629.1
TMEM69	NM_016486.4 link	c.*683C>T	downstream_gene_variant		ENST00000372025.5	NP_057570.2	Q5SWH9

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
IPP	ENST00000359942.8 link	c.1652-73G>A	intron_variant	Intron 9 of 9	1		ENSP00000353024.4	Q9Y573-2
TMEM69	ENST00000372025.5 link	c.*683C>T	downstream_gene_variant		1	NM_016486.4	ENSP00000361095.4	Q5SWH9
ENSG00000230896	ENST00000430643.1 link	n.*96G>A	downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.283

AC:

43032

AN:

151888

Hom.:

6216

Cov.:

show subpopulations

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.:

AF XY:

0.305

AC XY:

106834

AN XY:

349810

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

6731

13462

20192

26923

33654

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1834

3668

5502

7336

9170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.283

AC:

43091

AN:

152006

Hom.:

6236

Cov.:

AF XY:

0.284

AC XY:

21086

AN XY:

74274

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1573

3146

4720

6293

7866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

448

896

1344

1792

2240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.2

(source)

DANN

Benign

0.56

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over