rs2241598

Variant names:

• chr5-438449-T-C
• rs2241598
• NM_001377236.1:c.*3615T>C

Variant summary

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

The NM_001377236.1(AHRR):​c.*3615T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,190 control chromosomes in the GnomAD database, including 48,295 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 0.79 (48295 hom., cov: 34)
• Consequence: AHRR NM_001377236.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97
• Publications: 13 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.865 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.*3615T>C		downstream_gene	N/A	NP_001364165.1
	AHRR	NM_001377239.1		c.*3615T>C		downstream_gene	N/A	NP_001364168.1
	PDCD6-AHRR	NR_165159.2		n.*164T>C		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	ENST00000684583.1	MANE Select	c.*3615T>C		downstream_gene	N/A	ENSP00000507476.1
	AHRR	ENST00000316418.10	TSL:1	c.*3615T>C		downstream_gene	N/A	ENSP00000323816.6
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*5705T>C		downstream_gene	N/A	ENSP00000424601.2

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120388 AN: 152072 Hom.: 48271 Cov.: 34

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.792 AC: 120468 AN: 152190 Hom.: 48295 Cov.: 34 AF XY: 0.789 AC XY: 58695 AN XY: 74420

African (AFR) AF: 0.872 AC: 36231 AN: 41536

American (AMR) AF: 0.693 AC: 10599 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2518 AN: 3470

East Asian (EAS) AF: 0.448 AC: 2310 AN: 5154

South Asian (SAS) AF: 0.724 AC: 3493 AN: 4824

European-Finnish (FIN) AF: 0.863 AC: 9149 AN: 10604

Middle Eastern (MID) AF: 0.738 AC: 214 AN: 290

European-Non Finnish (NFE) AF: 0.789 AC: 53650 AN: 67998

Other (OTH) AF: 0.762 AC: 1610 AN: 2112

Alfa AF: 0.783 Hom.: 79094

Bravo AF: 0.785

Asia WGS AF: 0.641 AC: 2232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.019
DANN	Benign	0.37
PhyloP100		-3.0

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2241598; hg19: chr5-438564;