NM_001377236.1:c.908+115C>A

Variant names:

• chr5-428121-C-A
• rs12188164
• NM_001377236.1:c.908+115C>A

Variant summary

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

The NM_001377236.1(AHRR):​c.908+115C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,225,110 control chromosomes in the GnomAD database, including 82,016 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 0.26 (6894 hom., cov: 34)
  • Exomes 𝑓: 0.36 (75122 hom.)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• Publications: 37 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 = 0.384 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.908+115C>A		intron	N/A	NP_001364165.1
	AHRR	NM_001377239.1		c.908+115C>A		intron	N/A	NP_001364168.1
	PDCD6-AHRR	NR_165159.2		n.1255+115C>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	ENST00000684583.1	MANE Select	c.908+115C>A		intron	N/A	ENSP00000507476.1
	AHRR	ENST00000316418.10	TSL:1	c.908+115C>A		intron	N/A	ENSP00000323816.6
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*904+115C>A		intron	N/A	ENSP00000424601.2

Frequencies

GnomAD3 genomes AF: 0.264 AC: 40128 AN: 152004 Hom.: 6894 Cov.: 34

Gnomad AFR AF: 0.0701

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.00519

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.388

Gnomad OTH AF: 0.259

GnomAD4 exome AF: 0.358 AC: 384580 AN: 1072988 Hom.: 75122 AF XY: 0.355 AC XY: 189875 AN XY: 535012

African (AFR) AF: 0.0541 AC: 1315 AN: 24310

American (AMR) AF: 0.267 AC: 7964 AN: 29870

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 5106 AN: 21128

East Asian (EAS) AF: 0.00147 AC: 50 AN: 33918

South Asian (SAS) AF: 0.239 AC: 16090 AN: 67438

European-Finnish (FIN) AF: 0.397 AC: 18524 AN: 46658

Middle Eastern (MID) AF: 0.168 AC: 636 AN: 3790

European-Non Finnish (NFE) AF: 0.400 AC: 319876 AN: 799198

Other (OTH) AF: 0.322 AC: 15019 AN: 46678

GnomAD4 genome AF: 0.264 AC: 40131 AN: 152122 Hom.: 6894 Cov.: 34 AF XY: 0.260 AC XY: 19354 AN XY: 74344

African (AFR) AF: 0.0699 AC: 2906 AN: 41566

American (AMR) AF: 0.245 AC: 3741 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.246 AC: 852 AN: 3468

East Asian (EAS) AF: 0.00520 AC: 27 AN: 5192

South Asian (SAS) AF: 0.225 AC: 1085 AN: 4822

European-Finnish (FIN) AF: 0.394 AC: 4147 AN: 10532

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.388 AC: 26362 AN: 67948

Other (OTH) AF: 0.258 AC: 544 AN: 2112

Alfa AF: 0.332 Hom.: 33388

Bravo AF: 0.244

Asia WGS AF: 0.0990 AC: 343 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	0.93
DANN	Benign	0.52
PhyloP100		-0.39
PromoterAI		-0.045	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs12188164; hg19: chr5-428236;