rs7731963

Variant names:

• chr5-385899-A-C
• rs7731963
• NM_001377236.1:c.351+9183A>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+9183A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,794 control chromosomes in the GnomAD database, including 23,018 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 0.55 (23018 hom., cov: 32)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.351+9183A>C		intron_variant	Intron 4 of 10	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.351+9183A>C		intron_variant	Intron 4 of 10		NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.644+9183A>C		intron_variant	Intron 6 of 13
PDCD6-AHRR	NR_165163.2	n.644+9183A>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+9183A>C		intron_variant	Intron 4 of 10		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*347+9183A>C		intron_variant	Intron 6 of 13			ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82795 AN: 151676 Hom.: 23012 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.546 AC: 82832 AN: 151794 Hom.: 23018 Cov.: 32 AF XY: 0.545 AC XY: 40446 AN XY: 74200

African (AFR) AF: 0.523 AC: 21656 AN: 41382

American (AMR) AF: 0.469 AC: 7162 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1841 AN: 3460

East Asian (EAS) AF: 0.273 AC: 1405 AN: 5146

South Asian (SAS) AF: 0.599 AC: 2880 AN: 4810

European-Finnish (FIN) AF: 0.613 AC: 6439 AN: 10506

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.586 AC: 39793 AN: 67906

Other (OTH) AF: 0.504 AC: 1063 AN: 2110

Alfa AF: 0.578 Hom.: 14024

Bravo AF: 0.529

Asia WGS AF: 0.436 AC: 1512 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.46
PhyloP100		-0.57
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: rs7731963; hg19: chr5-386014;