ENST00000505113.6:n.*5243G>T – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000505113.6(PDCD6-AHRR):n.*5243G>T 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 0.755 in 152,328 control chromosomes in the GnomAD database, including 43,924 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 0.76 ( 43886 hom., cov: 34)

Exomes 𝑓: 0.73 ( 38 hom. )

Consequence

PDCD6-AHRR
ENST00000505113.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.449

Publications

31 publications found

Variant links:

Genes affected

PDCD6-AHRR (HGNC:54724): (PDCD6-AHRR readthrough (NMD candidate)) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PDCD6-AHRR links:

AHRR (HGNC:346): (aryl hydrocarbon receptor repressor) The protein encoded by this gene participates in the aryl hydrocarbon receptor (AhR) signaling cascade, which mediates dioxin toxicity, and is involved in regulation of cell growth and differentiation. It functions as a feedback modulator by repressing AhR-dependent gene expression. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jun 2011]

AHRR 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=-0.86).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AHRR	NM_001377236.1 link	c.*3153G>T	3_prime_UTR_variant	Exon 11 of 11	ENST00000684583.1	NP_001364165.1
PDCD6-AHRR	NR_165159.2 link	n.5594G>T	non_coding_transcript_exon_variant	Exon 14 of 14
PDCD6-AHRR	NR_165163.2 link	n.5540G>T	non_coding_transcript_exon_variant	Exon 13 of 13
AHRR	NM_001377239.1 link	c.*3153G>T	3_prime_UTR_variant	Exon 11 of 11		NP_001364168.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PDCD6-AHRR	ENST00000675395.1 link	n.*5297G>T	non_coding_transcript_exon_variant	Exon 14 of 14		ENSP00000502570.1	A0A6Q8PH81
AHRR	ENST00000684583.1 link	c.*3153G>T	3_prime_UTR_variant	Exon 11 of 11	NM_001377236.1	ENSP00000507476.1	A0A7I2PK40
PDCD6-AHRR	ENST00000675395.1 link	n.*5297G>T	3_prime_UTR_variant	Exon 14 of 14		ENSP00000502570.1	A0A6Q8PH81

Frequencies

GnomAD3 genomes

AF:

0.755

AC:

114837

AN:

152064

Hom.:

43874

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.758

Gnomad AMR

AF:

0.640

Gnomad ASJ

AF:

0.742

Gnomad EAS

AF:

0.443

Gnomad SAS

AF:

0.727

Gnomad FIN

AF:

0.856

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.789

Gnomad OTH

AF:

0.732

GnomAD4 exome

AF:

0.726

AC:

106

AN:

146

Hom.:

Cov.:

AF XY:

0.690

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.717

AC:

AN:

138

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AF:

1.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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:

0.755

AC:

114902

AN:

152182

Hom.:

43886

Cov.:

AF XY:

0.753

AC XY:

56033

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.762

AC:

31606

AN:

41492

American (AMR)

AF:

0.639

AC:

9777

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.742

AC:

2576

AN:

3472

East Asian (EAS)

AF:

0.444

AC:

2295

AN:

5172

South Asian (SAS)

AF:

0.727

AC:

3516

AN:

4834

European-Finnish (FIN)

AF:

0.856

AC:

9066

AN:

10596

Middle Eastern (MID)

AF:

0.707

AC:

208

AN:

294

European-Non Finnish (NFE)

AF:

0.788

AC:

53622

AN:

68010

Other (OTH)

AF:

0.732

AC:

1546

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1419

2838

4258

5677

7096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

854

1708

2562

3416

4270

<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:

0.773

Hom.:

181269

Bravo

AF:

0.740

Asia WGS

AF:

0.624

AC:

2171

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

1.1

(source)

DANN

Benign

0.34

PhyloP100

-0.45

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over