Genetic Variant PIGO-AS1:n.295C>A (chr9-35098011-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000431804.1(PIGO-AS1):n.295C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,954 control chromosomes in the GnomAD database, including 16,577 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 0.45 ( 16576 hom., cov: 32)

Exomes 𝑓: 0.50 ( 1 hom. )

Consequence

PIGO-AS1
ENST00000431804.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.148

Publications

8 publications found

Variant links:

Genes affected

PIGO-AS1 (HGNC:55692): (PIGO antisense RNA 1)

PIGO-AS1 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=-0.82).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank
PIGO-AS1	NR_186491.1 link	n.369C>A	non_coding_transcript_exon_variant	Exon 2 of 2
PIGO-AS1	NR_186492.1 link	n.118-1106C>A	intron_variant	Intron 1 of 1
PIGO-AS1	NR_186493.1 link	n.117+1591C>A	intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PIGO-AS1	ENST00000431804.1 link	n.295C>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.452

AC:

68578

AN:

151826

Hom.:

16577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.305

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.531

Gnomad ASJ

AF:

0.409

Gnomad EAS

AF:

0.155

Gnomad SAS

AF:

0.346

Gnomad FIN

AF:

0.532

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.542

Gnomad OTH

AF:

0.469

GnomAD4 exome

AF:

0.500

AC:

AN:

Hom.:

Cov.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000000565104), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.451

AC:

68592

AN:

151944

Hom.:

16576

Cov.:

AF XY:

0.448

AC XY:

33263

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.305

AC:

12613

AN:

41412

American (AMR)

AF:

0.532

AC:

8129

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.409

AC:

1420

AN:

3470

East Asian (EAS)

AF:

0.156

AC:

803

AN:

5162

South Asian (SAS)

AF:

0.345

AC:

1661

AN:

4818

European-Finnish (FIN)

AF:

0.532

AC:

5601

AN:

10532

Middle Eastern (MID)

AF:

0.456

AC:

134

AN:

294

European-Non Finnish (NFE)

AF:

0.542

AC:

36846

AN:

67950

Other (OTH)

AF:

0.464

AC:

980

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1814

3627

5441

7254

9068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

620

1240

1860

2480

3100

<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:

0.518

Hom.:

15885

Bravo

AF:

0.449

Asia WGS

AF:

0.265

AC:

922

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.7

(source)

DANN

Benign

0.68

PhyloP100

0.15

Splicing

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

Publications

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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