5-371843-C-T

Variant names:

• chr5-371843-C-T
• rs908114
• NM_001377236.1:c.245-4767C>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.245-4767C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 152,104 control chromosomes in the GnomAD database, including 31,230 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 0.64 (31230 hom., cov: 33)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.823
• Publications: 12 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.245-4767C>T		intron_variant	Intron 3 of 10	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.245-4767C>T		intron_variant	Intron 3 of 10		NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.538-4767C>T		intron_variant	Intron 5 of 13
PDCD6-AHRR	NR_165163.2	n.538-4767C>T		intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.245-4767C>T		intron_variant	Intron 3 of 10		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*241-4767C>T		intron_variant	Intron 5 of 13			ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96667 AN: 151986 Hom.: 31214 Cov.: 33

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.563

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.579

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.595

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.636 AC: 96737 AN: 152104 Hom.: 31230 Cov.: 33 AF XY: 0.634 AC XY: 47163 AN XY: 74346

African (AFR) AF: 0.651 AC: 26992 AN: 41472

American (AMR) AF: 0.585 AC: 8942 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.579 AC: 2011 AN: 3472

East Asian (EAS) AF: 0.291 AC: 1503 AN: 5158

South Asian (SAS) AF: 0.596 AC: 2873 AN: 4824

European-Finnish (FIN) AF: 0.673 AC: 7121 AN: 10588

Middle Eastern (MID) AF: 0.561 AC: 165 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45286 AN: 67992

Other (OTH) AF: 0.632 AC: 1332 AN: 2108

Alfa AF: 0.652 Hom.: 122601

Bravo AF: 0.627

Asia WGS AF: 0.442 AC: 1537 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.89
PhyloP100		-0.82
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: rs908114; hg19: chr5-371958;