dbSNP rs895415: PAX8-AS1:n.858G>A (chr2-113265640-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000422956.6(PAX8-AS1):n.858G>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 0.389 in 151,922 control chromosomes in the GnomAD database, including 11,759 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 0.39 ( 11752 hom., cov: 31)

Exomes 𝑓: 0.46 ( 7 hom. )

Consequence

PAX8-AS1
ENST00000422956.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.377

Publications

12 publications found

Variant links:

Genes affected

PAX8-AS1 (HGNC:49271): (PAX8 antisense RNA 1)

PAX8-AS1 links:

PAX8 (HGNC:8622): (paired box 8) This gene encodes a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins that contain a paired box domain, an octapeptide, and a paired-type homeodomain. This nuclear protein is involved in thyroid follicular cell development and expression of thyroid-specific genes. Mutations in this gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas and atypical follicular thyroid adenomas. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Mar 2010]

PAX8 Gene-Disease associations (from GenCC):

hypothyroidism, congenital, nongoitrous, 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
athyreosis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
thyroid hypoplasia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PAX8 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=-0.68).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PAX8	NM_003466.4 link	c.25+12730C>T		intron_variant	Intron 2 of 11	ENST00000429538.8	NP_003457.1	Q06710-1R9W7C9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PAX8	ENST00000429538.8 link	c.25+12730C>T		intron_variant	Intron 2 of 11	1	NM_003466.4	ENSP00000395498.3		Q06710-1

Frequencies

GnomAD3 genomes

AF:

0.389

AC:

59072

AN:

151758

Hom.:

11742

Cov.:

show subpopulations

Gnomad AFR

AF:

0.435

Gnomad AMI

AF:

0.465

Gnomad AMR

AF:

0.337

Gnomad ASJ

AF:

0.329

Gnomad EAS

AF:

0.109

Gnomad SAS

AF:

0.289

Gnomad FIN

AF:

0.418

Gnomad MID

AF:

0.244

Gnomad NFE

AF:

0.400

Gnomad OTH

AF:

0.380

GnomAD4 exome

AF:

0.457

AC:

AN:

Hom.:

Cov.:

AF XY:

0.321

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.550

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.450

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.389

AC:

59114

AN:

151876

Hom.:

11752

Cov.:

AF XY:

0.386

AC XY:

28675

AN XY:

74232

show subpopulations

African (AFR)

AF:

0.435

AC:

17976

AN:

41344

American (AMR)

AF:

0.337

AC:

5138

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.329

AC:

1142

AN:

3472

East Asian (EAS)

AF:

0.109

AC:

563

AN:

5172

South Asian (SAS)

AF:

0.289

AC:

1391

AN:

4812

European-Finnish (FIN)

AF:

0.418

AC:

4413

AN:

10560

Middle Eastern (MID)

AF:

0.238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.400

AC:

27195

AN:

67948

Other (OTH)

AF:

0.382

AC:

803

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1838

3677

5515

7354

9192

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

552

1104

1656

2208

2760

<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:

0.391

Hom.:

15141

Bravo

AF:

0.385

Asia WGS

AF:

0.249

AC:

868

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

8.2

(source)

DANN

Benign

0.82

PhyloP100

0.38

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over