rs3734145

Variant names:

• chr5-346521-A-G
• rs3734145
• NM_001377236.1:c.62+2557A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001377236.1(AHRR):​c.62+2557A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.692 in 152,126 control chromosomes in the GnomAD database, including 36,941 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 0.69 (36941 hom., cov: 33)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.332
• 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.62+2557A>G		intron_variant	Intron 2 of 10	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.62+2557A>G		intron_variant	Intron 2 of 10		NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.355+2557A>G		intron_variant	Intron 4 of 13
PDCD6-AHRR	NR_165163.2	n.355+2557A>G		intron_variant	Intron 4 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.62+2557A>G		intron_variant	Intron 2 of 10		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*58+2557A>G		intron_variant	Intron 4 of 13			ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.692 AC: 105180 AN: 152008 Hom.: 36907 Cov.: 33

Gnomad AFR AF: 0.714

Gnomad AMI AF: 0.768

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.301

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.696

Gnomad MID AF: 0.637

Gnomad NFE AF: 0.728

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.692 AC: 105277 AN: 152126 Hom.: 36941 Cov.: 33 AF XY: 0.688 AC XY: 51182 AN XY: 74378

African (AFR) AF: 0.714 AC: 29610 AN: 41474

American (AMR) AF: 0.627 AC: 9595 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2130 AN: 3472

East Asian (EAS) AF: 0.301 AC: 1560 AN: 5178

South Asian (SAS) AF: 0.655 AC: 3157 AN: 4820

European-Finnish (FIN) AF: 0.696 AC: 7376 AN: 10598

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.728 AC: 49498 AN: 67982

Other (OTH) AF: 0.698 AC: 1470 AN: 2106

Alfa AF: 0.712 Hom.: 23737

Bravo AF: 0.683

Asia WGS AF: 0.484 AC: 1685 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	13
DANN	Benign	0.45
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.25		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.25		Position offset: 1

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

Other links and lift over

dbSNP: rs3734145; hg19: chr5-346636;