Genetic Variant PDCD6-AHRR:n.*5003G>C (chr5-437747-G-C) – 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.*5003G>C 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 0.265 in 152,422 control chromosomes in the GnomAD database, including 6,984 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 0.26 ( 6975 hom., cov: 33)

Exomes 𝑓: 0.34 ( 9 hom. )

Consequence

PDCD6-AHRR
ENST00000505113.6 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.897

Publications

8 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:

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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 = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AHRR	NM_001377236.1 link	c.*2913G>C	3_prime_UTR_variant	Exon 11 of 11	ENST00000684583.1	NP_001364165.1
PDCD6-AHRR	NR_165159.2 link	n.5354G>C	non_coding_transcript_exon_variant	Exon 14 of 14
PDCD6-AHRR	NR_165163.2 link	n.5300G>C	non_coding_transcript_exon_variant	Exon 13 of 13
AHRR	NM_001377239.1 link	c.*2913G>C	3_prime_UTR_variant	Exon 11 of 11		NP_001364168.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
PDCD6-AHRR	ENST00000675395.1 link	n.*5057G>C	non_coding_transcript_exon_variant	Exon 14 of 14		ENSP00000502570.1
AHRR	ENST00000684583.1 link	c.*2913G>C	3_prime_UTR_variant	Exon 11 of 11	NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1 link	n.*5057G>C	3_prime_UTR_variant	Exon 14 of 14		ENSP00000502570.1

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40326

AN:

152162

Hom.:

6975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0704

Gnomad AMI

AF:

0.476

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.224

Gnomad FIN

AF:

0.396

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.260

GnomAD4 exome

AF:

0.338

AC:

AN:

142

Hom.:

Cov.:

AF XY:

0.256

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.289

AC:

AN:

114

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.700

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.357

AC:

AN:

Other (OTH)

AF:

0.750

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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:

0.265

AC:

40329

AN:

152280

Hom.:

6975

Cov.:

AF XY:

0.262

AC XY:

19479

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.0701

AC:

2915

AN:

41560

American (AMR)

AF:

0.246

AC:

3761

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

854

AN:

3470

East Asian (EAS)

AF:

0.00520

AC:

AN:

5192

South Asian (SAS)

AF:

0.226

AC:

1090

AN:

4830

European-Finnish (FIN)

AF:

0.396

AC:

4200

AN:

10598

Middle Eastern (MID)

AF:

0.122

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.389

AC:

26465

AN:

68010

Other (OTH)

AF:

0.259

AC:

547

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1416

2832

4247

5663

7079

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.159

Hom.:

360

Bravo

AF:

0.245

Asia WGS

AF:

0.0990

AC:

343

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

5.1

(source)

DANN

Benign

0.61

PhyloP100

0.90

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