rs2721020

Variant names:

• chr5-379083-T-C
• rs2721020
• NM_001377236.1:c.351+2367T>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.351+2367T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.745 in 152,130 control chromosomes in the GnomAD database, including 42,951 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 0.75 (42951 hom., cov: 33)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04
• Publications: 10 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 = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.351+2367T>C		intron_variant	Intron 4 of 10	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.351+2367T>C		intron_variant	Intron 4 of 10		NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.644+2367T>C		intron_variant	Intron 6 of 13
PDCD6-AHRR	NR_165163.2	n.644+2367T>C		intron_variant	Intron 6 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.351+2367T>C		intron_variant	Intron 4 of 10		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*347+2367T>C		intron_variant	Intron 6 of 13			ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113249 AN: 152012 Hom.: 42918 Cov.: 33

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.840

Gnomad AMR AF: 0.656

Gnomad ASJ AF: 0.659

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.711

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.658

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.722

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

GnomAD4 genome AF: 0.745 AC: 113347 AN: 152130 Hom.: 42951 Cov.: 33 AF XY: 0.743 AC XY: 55287 AN XY: 74374

African (AFR) AF: 0.781 AC: 32414 AN: 41492

American (AMR) AF: 0.656 AC: 10030 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.659 AC: 2287 AN: 3470

East Asian (EAS) AF: 0.293 AC: 1515 AN: 5164

South Asian (SAS) AF: 0.712 AC: 3435 AN: 4824

European-Finnish (FIN) AF: 0.821 AC: 8687 AN: 10586

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52508 AN: 67994

Other (OTH) AF: 0.720 AC: 1513 AN: 2102

Alfa AF: 0.749 Hom.: 80152

Bravo AF: 0.730

Asia WGS AF: 0.514 AC: 1789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.47
DANN	Benign	0.34
PhyloP100		-2.0
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: rs2721020; hg19: chr5-379198;