chr5-392890-T-C

Variant names:

• chr5-392890-T-C
• rs2671903
• NM_001377236.1:c.351+16174T>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+16174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,818 control chromosomes in the GnomAD database, including 12,421 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 0.33 (12421 hom., cov: 31)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 1 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	NM_001377236.1	MANE Select	c.351+16174T>C		intron	N/A	NP_001364165.1
	AHRR	NM_001377239.1		c.351+16174T>C		intron	N/A	NP_001364168.1
	PDCD6-AHRR	NR_165159.2		n.644+16174T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	ENST00000684583.1	MANE Select	c.351+16174T>C		intron	N/A	ENSP00000507476.1
	AHRR	ENST00000316418.10	TSL:1	c.351+16174T>C		intron	N/A	ENSP00000323816.6
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*347+16174T>C		intron	N/A	ENSP00000424601.2

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50202 AN: 151700 Hom.: 12388 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.331 AC: 50289 AN: 151818 Hom.: 12421 Cov.: 31 AF XY: 0.325 AC XY: 24108 AN XY: 74218

African (AFR) AF: 0.699 AC: 28843 AN: 41278

American (AMR) AF: 0.244 AC: 3722 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 677 AN: 3466

East Asian (EAS) AF: 0.0419 AC: 217 AN: 5174

South Asian (SAS) AF: 0.127 AC: 611 AN: 4798

European-Finnish (FIN) AF: 0.198 AC: 2094 AN: 10582

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.193 AC: 13082 AN: 67954

Other (OTH) AF: 0.312 AC: 655 AN: 2102

Alfa AF: 0.280 Hom.: 1096

Bravo AF: 0.352

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.14
PhyloP100		-0.90
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: rs2671903; hg19: chr5-393005;