chr5-360428-C-T

Variant names:

• chr5-360428-C-T
• rs6555205
• NM_001377236.1:c.244+6517C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377236.1(AHRR):​c.244+6517C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 152,082 control chromosomes in the GnomAD database, including 19,933 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 0.51 (19933 hom., cov: 33)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.442
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	NM_001377236.1	MANE Select	c.244+6517C>T		intron	N/A	NP_001364165.1
	AHRR	NM_001377239.1		c.244+6517C>T		intron	N/A	NP_001364168.1
	PDCD6-AHRR	NR_165159.2		n.537+6517C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	ENST00000684583.1	MANE Select	c.244+6517C>T		intron	N/A	ENSP00000507476.1
	AHRR	ENST00000316418.10	TSL:1	c.244+6517C>T		intron	N/A	ENSP00000323816.6
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*240+6517C>T		intron	N/A	ENSP00000424601.2

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77228 AN: 151964 Hom.: 19926 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.524

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.502

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

GnomAD4 genome AF: 0.508 AC: 77265 AN: 152082 Hom.: 19933 Cov.: 33 AF XY: 0.504 AC XY: 37475 AN XY: 74326

African (AFR) AF: 0.520 AC: 21555 AN: 41472

American (AMR) AF: 0.462 AC: 7064 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1688 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1442 AN: 5176

South Asian (SAS) AF: 0.524 AC: 2523 AN: 4814

European-Finnish (FIN) AF: 0.472 AC: 4985 AN: 10568

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36433 AN: 67992

Other (OTH) AF: 0.506 AC: 1066 AN: 2108

Alfa AF: 0.529 Hom.: 57690

Bravo AF: 0.504

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-0.44
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: rs6555205; hg19: chr5-360543;