5-434866-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000505113.6(PDCD6-AHRR):​n.*2122G>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
  • Failed GnomAD Quality Control
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.*32G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000684583.1	NP_001364165.1
PDCD6-AHRR	NR_165159.2	n.2473G>T		non_coding_transcript_exon_variant	Exon 14 of 14
PDCD6-AHRR	NR_165163.2	n.2419G>T		non_coding_transcript_exon_variant	Exon 13 of 13
AHRR	NM_001377239.1	c.*32G>T		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>T		non_coding_transcript_exon_variant	Exon 14 of 14			ENSP00000502570.1
AHRR	ENST00000684583.1	c.*32G>T		3_prime_UTR_variant	Exon 11 of 11		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*2176G>T		3_prime_UTR_variant	Exon 14 of 14			ENSP00000502570.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.32e-7 AC: 1 AN: 1365470 Hom.: 0 Cov.: 61 AF XY: 0.00 AC XY: 0 AN XY: 667998

African (AFR) AF: 0.0000319 AC: 1 AN: 31308

American (AMR) AF: 0.00 AC: 0 AN: 34690

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23112

East Asian (EAS) AF: 0.00 AC: 0 AN: 35602

South Asian (SAS) AF: 0.00 AC: 0 AN: 74638

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46804

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4184

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1058630

Other (OTH) AF: 0.00 AC: 0 AN: 56502

GnomAD4 genome Cov.: 34

Alfa AF: 0.00 Hom.: 6623

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.4
DANN	Benign	0.20
PhyloP100		-2.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;