5-373423-A-G

Variant names:

• chr5-373423-A-G
• rs6894195
• NM_001377236.1:c.245-3187A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377236.1(AHRR):​c.245-3187A>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
• Publications: 2 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=-0.95).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	NM_001377236.1	MANE Select	c.245-3187A>G		intron	N/A	NP_001364165.1
	AHRR	NM_001377239.1		c.245-3187A>G		intron	N/A	NP_001364168.1
	PDCD6-AHRR	NR_165159.2		n.538-3187A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	ENST00000684583.1	MANE Select	c.245-3187A>G		intron	N/A	ENSP00000507476.1
	AHRR	ENST00000316418.10	TSL:1	c.245-3187A>G		intron	N/A	ENSP00000323816.6
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*241-3187A>G		intron	N/A	ENSP00000424601.2

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

African (AFR) AF: 0.0253 AC: 1053 AN: 41540

American (AMR) AF: 0.109 AC: 1670 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0882 AC: 306 AN: 3470

East Asian (EAS) AF: 0.0198 AC: 102 AN: 5164

South Asian (SAS) AF: 0.0564 AC: 272 AN: 4822

European-Finnish (FIN) AF: 0.176 AC: 1870 AN: 10608

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

European-Non Finnish (NFE) AF: 0.121 AC: 8192 AN: 67940

Other (OTH) AF: 0.106 AC: 224 AN: 2114

Alfa AF: 0.0671 Hom.: 104

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	-0.95
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6894195; hg19: chr5-373538;