5-373423-A-G

Position:

• chr5-373423-A-G

Variant summary

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

The NM_001377236.1(AHRR):​c.245-3187A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.091 in 152,164 control chromosomes in the GnomAD database, including 880 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 0.091 (880 hom., cov: 33)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.245-3187A>G		intron_variant		ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.245-3187A>G		intron_variant			NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.538-3187A>G		intron_variant
PDCD6-AHRR	NR_165163.2	n.538-3187A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.245-3187A>G		intron_variant			NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*241-3187A>G		intron_variant				ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.0910 AC: 13842 AN: 152046 Hom.: 880 Cov.: 33

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0882

Gnomad EAS AF: 0.0197

Gnomad SAS AF: 0.0559

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.107

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0910 AC: 13840 AN: 152164 Hom.: 880 Cov.: 33 AF XY: 0.0930 AC XY: 6916 AN XY: 74392

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0882

Gnomad4 EAS AF: 0.0198

Gnomad4 SAS AF: 0.0564

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.121

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0674 Hom.: 103

Bravo AF: 0.0830

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.5
DANN	Benign	0.37

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: rs6894195; hg19: chr5-373538;