rs6887387

Variant names:

• chr5-344103-C-T
• rs6887387
• NM_001377236.1:c.62+139C>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.62+139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 859,742 control chromosomes in the GnomAD database, including 135,475 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 (23442 hom., cov: 27)
  • Exomes 𝑓: 0.56 (112033 hom.)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 7 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 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.62+139C>T		intron	N/A	NP_001364165.1	A0A7I2PK40
	AHRR	NM_001377239.1		c.62+139C>T		intron	N/A	NP_001364168.1	A0A7I2PK40
	PDCD6-AHRR	NR_165159.2		n.355+139C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	ENST00000684583.1	MANE Select	c.62+139C>T		intron	N/A	ENSP00000507476.1	A0A7I2PK40
	AHRR	ENST00000316418.10	TSL:1	c.62+139C>T		intron	N/A	ENSP00000323816.6	A0A7I2PK40
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*58+139C>T		intron	N/A	ENSP00000424601.2	A0A6Q8PH81

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83378 AN: 150790 Hom.: 23428 Cov.: 27

Gnomad AFR AF: 0.622

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.532

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.554

Gnomad OTH AF: 0.554

GnomAD4 exome AF: 0.559 AC: 396276 AN: 708844 Hom.: 112033 AF XY: 0.558 AC XY: 205510 AN XY: 368540

African (AFR) AF: 0.637 AC: 8342 AN: 13106

American (AMR) AF: 0.476 AC: 5785 AN: 12144

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 10084 AN: 17214

East Asian (EAS) AF: 0.379 AC: 9253 AN: 24442

South Asian (SAS) AF: 0.551 AC: 30446 AN: 55296

European-Finnish (FIN) AF: 0.502 AC: 16840 AN: 33558

Middle Eastern (MID) AF: 0.591 AC: 1705 AN: 2886

European-Non Finnish (NFE) AF: 0.571 AC: 295121 AN: 516432

Other (OTH) AF: 0.554 AC: 18700 AN: 33766

GnomAD4 genome AF: 0.553 AC: 83438 AN: 150898 Hom.: 23442 Cov.: 27 AF XY: 0.548 AC XY: 40394 AN XY: 73646

African (AFR) AF: 0.621 AC: 25563 AN: 41142

American (AMR) AF: 0.500 AC: 7619 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1974 AN: 3460

East Asian (EAS) AF: 0.289 AC: 1409 AN: 4878

South Asian (SAS) AF: 0.532 AC: 2543 AN: 4784

European-Finnish (FIN) AF: 0.487 AC: 5087 AN: 10448

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37502 AN: 67660

Other (OTH) AF: 0.557 AC: 1168 AN: 2098

Alfa AF: 0.547 Hom.: 2875

Bravo AF: 0.554

Asia WGS AF: 0.420 AC: 1457 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.3
DANN	Benign	0.83
PhyloP100		-0.049
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs6887387; hg19: chr5-344218; COSMIC: COSV100327107;