rs2672723

chr5-398423-A-Gchr5-398423-A-T

Variant summary

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

The NM_001377236.1(AHRR):c.352-14921A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 152,016 control chromosomes in the GnomAD database, including 2,999 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 0.19 (2999 hom., cov: 33)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.37

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AHRR	NM_001377236.1	c.352-14921A>G		intron_variant		ENST00000684583.1
PDCD6-AHRR	NR_165159.2	n.645-14921A>G		intron_variant, non_coding_transcript_variant
AHRR	NM_001377239.1	c.352-14921A>G		intron_variant
PDCD6-AHRR	NR_165163.2	n.645-14921A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHRR	ENST00000684583.1	c.352-14921A>G		intron_variant			NM_001377236.1	P1
AHRR	ENST00000316418.10	c.352-14921A>G		intron_variant		1		P1
AHRR	ENST00000510400.5	c.352-14921A>G		intron_variant		4
AHRR	ENST00000514523.1	c.-99-14921A>G		intron_variant		4

Frequencies

GnomAD3 genomes AF: 0.191 AC: 28948 AN: 151898 Hom.: 2990 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.347

Gnomad AMR AF: 0.178

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.0299

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.188

Gnomad OTH AF: 0.202

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

GnomAD4 genome AF: 0.191 AC: 28989 AN: 152016 Hom.: 2999 Cov.: 33 AF XY: 0.190 AC XY: 14116 AN XY: 74316

Gnomad4 AFR AF: 0.226

Gnomad4 AMR AF: 0.178

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.0300

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.188

Gnomad4 OTH AF: 0.199

Alfa AF: 0.185 Hom.: 357

Bravo AF: 0.189

Asia WGS AF: 0.0870 AC: 302 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.34
Dann	Benign	0.64

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: rs2672723; hg19: chr5-398538;