rs6887387

Positions:

• chr5-344103-C-T

Variant summary

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

The NM_001377236.1(AHRR):​c.62+139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 859,742 control chromosomes in the GnomAD database, including 135,475 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 0.55 (23442 hom., cov: 27)
  • Exomes 𝑓: 0.56 (112033 hom.)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490

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]

PDCD6-AHRR (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.62+139C>T		intron_variant		ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.62+139C>T		intron_variant			NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.355+139C>T		intron_variant
PDCD6-AHRR	NR_165163.2	n.355+139C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.62+139C>T		intron_variant			NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*58+139C>T		intron_variant				ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83378 AN: 150790 Hom.: 23428 Cov.: 27

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.559 AC: 396276 AN: 708844 Hom.: 112033 AF XY: 0.558 AC XY: 205510 AN XY: 368540

Gnomad4 AFR exome AF: 0.637

Gnomad4 AMR exome AF: 0.476

Gnomad4 ASJ exome AF: 0.586

Gnomad4 EAS exome AF: 0.379

Gnomad4 SAS exome AF: 0.551

Gnomad4 FIN exome AF: 0.502

Gnomad4 NFE exome AF: 0.571

Gnomad4 OTH exome AF: 0.554

GnomAD4 genome AF: 0.553 AC: 83438 AN: 150898 Hom.: 23442 Cov.: 27 AF XY: 0.548 AC XY: 40394 AN XY: 73646

Gnomad4 AFR AF: 0.621

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.487

Gnomad4 NFE AF: 0.554

Gnomad4 OTH AF: 0.557

Alfa AF: 0.547 Hom.: 2875

Bravo AF: 0.554

Asia WGS AF: 0.420 AC: 1457 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.83
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs6887387; hg19: chr5-344218; COSMIC: COSV100327107;