ENST00000505113.6:n.*2122G>C

Variant names:

• chr5-434866-G-C
• rs2672725
• ENST00000505113.6:n.*2122G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000505113.6(PDCD6-AHRR):​n.*2122G>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 0.865 in 1,517,626 control chromosomes in the GnomAD database, including 570,585 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 0.85 (55007 hom., cov: 34)
  • Exomes 𝑓: 0.87 (515578 hom.)
• Consequence: PDCD6-AHRR ENST00000505113.6 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05
• Publications: 22 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.*32G>C		3_prime_UTR_variant	Exon 11 of 11	ENST00000684583.1	NP_001364165.1
PDCD6-AHRR	NR_165159.2	n.2473G>C		non_coding_transcript_exon_variant	Exon 14 of 14
PDCD6-AHRR	NR_165163.2	n.2419G>C		non_coding_transcript_exon_variant	Exon 13 of 13
AHRR	NM_001377239.1	c.*32G>C		3_prime_UTR_variant	Exon 11 of 11		NP_001364168.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDCD6-AHRR	ENST00000675395.1	n.*2176G>C		non_coding_transcript_exon_variant	Exon 14 of 14			ENSP00000502570.1
AHRR	ENST00000684583.1	c.*32G>C		3_prime_UTR_variant	Exon 11 of 11		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*2176G>C		3_prime_UTR_variant	Exon 14 of 14			ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128941 AN: 152174 Hom.: 54984 Cov.: 34

Gnomad AFR AF: 0.841

Gnomad AMI AF: 0.866

Gnomad AMR AF: 0.778

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.571

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.921

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.882

Gnomad OTH AF: 0.845

GnomAD2 exomes AF: 0.823 AC: 113511 AN: 137930 AF XY: 0.824

Gnomad AFR exome AF: 0.847

Gnomad AMR exome AF: 0.773

Gnomad ASJ exome AF: 0.844

Gnomad EAS exome AF: 0.576

Gnomad FIN exome AF: 0.919

Gnomad NFE exome AF: 0.879

Gnomad OTH exome AF: 0.831

GnomAD4 exome AF: 0.867 AC: 1183265 AN: 1365334 Hom.: 515578 Cov.: 61 AF XY: 0.865 AC XY: 577909 AN XY: 667924

African (AFR) AF: 0.839 AC: 26282 AN: 31308

American (AMR) AF: 0.777 AC: 26939 AN: 34680

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 19397 AN: 23098

East Asian (EAS) AF: 0.546 AC: 19452 AN: 35598

South Asian (SAS) AF: 0.795 AC: 59349 AN: 74616

European-Finnish (FIN) AF: 0.916 AC: 42883 AN: 46794

Middle Eastern (MID) AF: 0.825 AC: 3450 AN: 4184

European-Non Finnish (NFE) AF: 0.885 AC: 937347 AN: 1058562

Other (OTH) AF: 0.853 AC: 48166 AN: 56494

GnomAD4 genome AF: 0.847 AC: 129017 AN: 152292 Hom.: 55007 Cov.: 34 AF XY: 0.845 AC XY: 62943 AN XY: 74458

African (AFR) AF: 0.840 AC: 34917 AN: 41550

American (AMR) AF: 0.778 AC: 11899 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2916 AN: 3470

East Asian (EAS) AF: 0.571 AC: 2961 AN: 5182

South Asian (SAS) AF: 0.777 AC: 3749 AN: 4826

European-Finnish (FIN) AF: 0.921 AC: 9777 AN: 10616

Middle Eastern (MID) AF: 0.830 AC: 244 AN: 294

European-Non Finnish (NFE) AF: 0.882 AC: 59981 AN: 68026

Other (OTH) AF: 0.843 AC: 1783 AN: 2114

Alfa AF: 0.863 Hom.: 6623

Bravo AF: 0.838

Asia WGS AF: 0.717 AC: 2496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.40
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2672725; hg19: chr5-434981; COSMIC: COSV57082410; COSMIC: COSV57082410;