rs2671903

Positions:

• chr5-392890-T-C

Variant summary

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

The NM_001377236.1(AHRR):​c.351+16174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,818 control chromosomes in the GnomAD database, including 12,421 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 0.33 (12421 hom., cov: 31)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900

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:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.351+16174T>C		intron_variant		ENST00000684583.1	NP_001364165.1
PDCD6-AHRR	NR_165159.2	n.644+16174T>C		intron_variant, non_coding_transcript_variant
AHRR	NM_001377239.1	c.351+16174T>C		intron_variant			NP_001364168.1
PDCD6-AHRR	NR_165163.2	n.644+16174T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.351+16174T>C		intron_variant			NM_001377236.1	ENSP00000507476	P1
AHRR	ENST00000316418.10	c.351+16174T>C		intron_variant		1		ENSP00000323816	P1
AHRR	ENST00000510400.5	c.351+16174T>C		intron_variant		4		ENSP00000428893
AHRR	ENST00000514523.1	c.-100+16174T>C		intron_variant		4		ENSP00000430914

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50202 AN: 151700 Hom.: 12388 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0418

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.315

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

GnomAD4 genome AF: 0.331 AC: 50289 AN: 151818 Hom.: 12421 Cov.: 31 AF XY: 0.325 AC XY: 24108 AN XY: 74218

Gnomad4 AFR AF: 0.699

Gnomad4 AMR AF: 0.244

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0419

Gnomad4 SAS AF: 0.127

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.312

Alfa AF: 0.280 Hom.: 1096

Bravo AF: 0.352

Asia WGS AF: 0.129 AC: 449 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.30
DANN	Benign	0.14

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

Publications

LitVar

Other links and lift over

dbSNP: rs2671903; hg19: chr5-393005;