rs6869832

Positions:

• chr5-373185-G-A

Variant summary

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

The NM_001377236.1(AHRR):​c.245-3425G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0909 in 152,292 control chromosomes in the GnomAD database, including 881 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 (881 hom., cov: 33)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• 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.245-3425G>A		intron_variant		ENST00000684583.1	NP_001364165.1
PDCD6-AHRR	NR_165159.2	n.538-3425G>A		intron_variant, non_coding_transcript_variant
AHRR	NM_001377239.1	c.245-3425G>A		intron_variant			NP_001364168.1
PDCD6-AHRR	NR_165163.2	n.538-3425G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.245-3425G>A		intron_variant			NM_001377236.1	ENSP00000507476	P1
AHRR	ENST00000316418.10	c.245-3425G>A		intron_variant		1		ENSP00000323816	P1
AHRR	ENST00000510400.5	c.245-3425G>A		intron_variant		4		ENSP00000428893
AHRR	ENST00000514523.1	c.-206-3425G>A		intron_variant		4		ENSP00000430914

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13840 AN: 152174 Hom.: 881 Cov.: 33

Gnomad AFR AF: 0.0254

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.176

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.120

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.0909 AC: 13838 AN: 152292 Hom.: 881 Cov.: 33 AF XY: 0.0928 AC XY: 6912 AN XY: 74460

Gnomad4 AFR AF: 0.0253

Gnomad4 AMR AF: 0.109

Gnomad4 ASJ AF: 0.0878

Gnomad4 EAS AF: 0.0197

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.176

Gnomad4 NFE AF: 0.120

Gnomad4 OTH AF: 0.106

Alfa AF: 0.112 Hom.: 155

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	-0.80
CADD	Benign	7.0
DANN	Benign	0.50

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

Publications

LitVar

Other links and lift over

dbSNP: rs6869832; hg19: chr5-373300;