rs6869832

Variant names:

• chr5-373185-G-A
• rs6869832
• NM_001377236.1:c.245-3425G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377236.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	NM_001377236.1	MANE Select	c.245-3425G>A		intron	N/A	NP_001364165.1	A0A7I2PK40
	AHRR	NM_001377239.1		c.245-3425G>A		intron	N/A	NP_001364168.1	A0A7I2PK40
	PDCD6-AHRR	NR_165159.2		n.538-3425G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	ENST00000684583.1	MANE Select	c.245-3425G>A		intron	N/A	ENSP00000507476.1	A0A7I2PK40
	AHRR	ENST00000316418.10	TSL:1	c.245-3425G>A		intron	N/A	ENSP00000323816.6	A0A7I2PK40
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*241-3425G>A		intron	N/A	ENSP00000424601.2	A0A6Q8PH81

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

African (AFR) AF: 0.0253 AC: 1053 AN: 41576

American (AMR) AF: 0.109 AC: 1670 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.0197 AC: 102 AN: 5186

South Asian (SAS) AF: 0.0563 AC: 272 AN: 4832

European-Finnish (FIN) AF: 0.176 AC: 1871 AN: 10602

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.120 AC: 8190 AN: 67998

Other (OTH) AF: 0.106 AC: 224 AN: 2116

Alfa AF: 0.110 Hom.: 156

Bravo AF: 0.0830

Asia WGS AF: 0.0340 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.0
DANN	Benign	0.50
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6869832; hg19: chr5-373300;