rs2241598

Variant names:

• chr5-438449-T-C
• rs2241598
• NM_001377236.1:c.*3615T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001377236.1(AHRR):​c.*3615T>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.792 in 152,190 control chromosomes in the GnomAD database, including 48,295 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 0.79 (48295 hom., cov: 34)
• Consequence: AHRR NM_001377236.1 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.97

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

Verdict is Benign. Variant got -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 = 0.865 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.*3615T>C		downstream_gene_variant		ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.*3615T>C		downstream_gene_variant			NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.*164T>C		downstream_gene_variant
PDCD6-AHRR	NR_165163.2	n.*164T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.*3615T>C		downstream_gene_variant			NM_001377236.1	ENSP00000507476.1
AHRR	ENST00000316418.10	c.*3615T>C		downstream_gene_variant		1		ENSP00000323816.6
PDCD6-AHRR	ENST00000505113.6	n.*5705T>C		downstream_gene_variant		1		ENSP00000424601.2
PDCD6-AHRR	ENST00000675395.1	n.*5759T>C		downstream_gene_variant				ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.792 AC: 120388 AN: 152072 Hom.: 48271 Cov.: 34

Gnomad AFR AF: 0.873

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.693

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.448

Gnomad SAS AF: 0.723

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.789

Gnomad OTH AF: 0.763

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

GnomAD4 genome AF: 0.792 AC: 120468 AN: 152190 Hom.: 48295 Cov.: 34 AF XY: 0.789 AC XY: 58695 AN XY: 74420

Gnomad4 AFR AF: 0.872

Gnomad4 AMR AF: 0.693

Gnomad4 ASJ AF: 0.726

Gnomad4 EAS AF: 0.448

Gnomad4 SAS AF: 0.724

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.789

Gnomad4 OTH AF: 0.762

Alfa AF: 0.779 Hom.: 62230

Bravo AF: 0.785

Asia WGS AF: 0.641 AC: 2232 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.019
DANN	Benign	0.37

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2241598; hg19: chr5-438564;