rs3734145

chr5-346521-A-G

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
AHRR	NM_001377236.1	c.62+2557A>G		intron_variant		ENST00000684583.1
PDCD6-AHRR	NR_165159.2	n.355+2557A>G		intron_variant, non_coding_transcript_variant
AHRR	NM_001377239.1	c.62+2557A>G		intron_variant
PDCD6-AHRR	NR_165163.2	n.355+2557A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHRR	ENST00000684583.1	c.62+2557A>G		intron_variant			NM_001377236.1	P1

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

Gnomad4 AFR AF: 0.714

Gnomad4 AMR AF: 0.627

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.655

Gnomad4 FIN AF: 0.696

Gnomad4 NFE AF: 0.728

Gnomad4 OTH AF: 0.698

Alfa AF: 0.711 Hom.: 21746

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs3734145; hg19: chr5-346636;