rs7731963

Positions:

• chr5-385899-A-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+9183A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,794 control chromosomes in the GnomAD database, including 23,018 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 (23018 hom., cov: 32)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

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 (SAS) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.351+9183A>C		intron_variant		ENST00000684583.1	NP_001364165.1
PDCD6-AHRR	NR_165159.2	n.644+9183A>C		intron_variant, non_coding_transcript_variant
AHRR	NM_001377239.1	c.351+9183A>C		intron_variant			NP_001364168.1
PDCD6-AHRR	NR_165163.2	n.644+9183A>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+9183A>C		intron_variant			NM_001377236.1	ENSP00000507476	P1
AHRR	ENST00000316418.10	c.351+9183A>C		intron_variant		1		ENSP00000323816	P1
AHRR	ENST00000510400.5	c.351+9183A>C		intron_variant		4		ENSP00000428893
AHRR	ENST00000514523.1	c.-100+9183A>C		intron_variant		4		ENSP00000430914

Frequencies

GnomAD3 genomes AF: 0.546 AC: 82795 AN: 151676 Hom.: 23012 Cov.: 32

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.492

Gnomad AMR AF: 0.469

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.598

Gnomad FIN AF: 0.613

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.546 AC: 82832 AN: 151794 Hom.: 23018 Cov.: 32 AF XY: 0.545 AC XY: 40446 AN XY: 74200

Gnomad4 AFR AF: 0.523

Gnomad4 AMR AF: 0.469

Gnomad4 ASJ AF: 0.532

Gnomad4 EAS AF: 0.273

Gnomad4 SAS AF: 0.599

Gnomad4 FIN AF: 0.613

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.504

Alfa AF: 0.579 Hom.: 12754

Bravo AF: 0.529

Asia WGS AF: 0.436 AC: 1512 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.89
DANN	Benign	0.46

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: rs7731963; hg19: chr5-386014;