chr5-428121-C-A

Position:

• chr5-428121-C-A

Variant summary

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

The NM_001377236.1(AHRR):​c.908+115C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,225,110 control chromosomes in the GnomAD database, including 82,016 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 (6894 hom., cov: 34)
  • Exomes 𝑓: 0.36 (75122 hom.)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.908+115C>A		intron_variant		ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.908+115C>A		intron_variant			NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.1255+115C>A		intron_variant
PDCD6-AHRR	NR_165163.2	n.1201+115C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.908+115C>A		intron_variant			NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*958+115C>A		intron_variant				ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40128 AN: 152004 Hom.: 6894 Cov.: 34

Gnomad AFR AF: 0.0701

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.358 AC: 384580 AN: 1072988 Hom.: 75122 AF XY: 0.355 AC XY: 189875 AN XY: 535012

Gnomad4 AFR exome AF: 0.0541

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.242

Gnomad4 EAS exome AF: 0.00147

Gnomad4 SAS exome AF: 0.239

Gnomad4 FIN exome AF: 0.397

Gnomad4 NFE exome AF: 0.400

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.264 AC: 40131 AN: 152122 Hom.: 6894 Cov.: 34 AF XY: 0.260 AC XY: 19354 AN XY: 74344

Gnomad4 AFR AF: 0.0699

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.00520

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.388

Gnomad4 OTH AF: 0.258

Alfa AF: 0.349 Hom.: 22269

Bravo AF: 0.244

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	-0.90
CADD	Benign	0.93
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12188164; hg19: chr5-428236;