5-434866-G-C

Position:

• chr5-434866-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377236.1(AHRR):​c.*32G>C variant causes a 3 prime UTR 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: AHRR NM_001377236.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.05

Genes affected

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]

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.*32G>C		3_prime_UTR_variant	11/11	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.*32G>C		3_prime_UTR_variant	11/11		NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.2473G>C		non_coding_transcript_exon_variant	14/14
PDCD6-AHRR	NR_165163.2	n.2419G>C		non_coding_transcript_exon_variant	13/13

Ensembl

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

GnomAD3 exomes AF: 0.823 AC: 113511 AN: 137930 Hom.: 47306 AF XY: 0.824 AC XY: 59296 AN XY: 71926

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 SAS exome AF: 0.789

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

Gnomad4 AFR exome AF: 0.839

Gnomad4 AMR exome AF: 0.777

Gnomad4 ASJ exome AF: 0.840

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.795

Gnomad4 FIN exome AF: 0.916

Gnomad4 NFE exome AF: 0.885

Gnomad4 OTH exome AF: 0.853

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

Gnomad4 AFR AF: 0.840

Gnomad4 AMR AF: 0.778

Gnomad4 ASJ AF: 0.840

Gnomad4 EAS AF: 0.571

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.921

Gnomad4 NFE AF: 0.882

Gnomad4 OTH AF: 0.843

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

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

LitVar

Other links and lift over

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