rs4957028

Variant names:

• chr5-361582-C-T
• rs4957028
• NM_001377236.1:c.244+7671C>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.244+7671C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.508 in 151,994 control chromosomes in the GnomAD database, including 19,933 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 0.51 (19933 hom., cov: 33)
• Consequence: AHRR NM_001377236.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.86
• Publications: 8 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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.244+7671C>T		intron_variant	Intron 3 of 10	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.244+7671C>T		intron_variant	Intron 3 of 10		NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.537+7671C>T		intron_variant	Intron 5 of 13
PDCD6-AHRR	NR_165163.2	n.537+7671C>T		intron_variant	Intron 5 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.244+7671C>T		intron_variant	Intron 3 of 10		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*240+7671C>T		intron_variant	Intron 5 of 13			ENSP00000502570.1

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77219 AN: 151876 Hom.: 19926 Cov.: 33

Gnomad AFR AF: 0.520

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.536

Gnomad OTH AF: 0.503

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

GnomAD4 genome AF: 0.508 AC: 77256 AN: 151994 Hom.: 19933 Cov.: 33 AF XY: 0.505 AC XY: 37495 AN XY: 74302

African (AFR) AF: 0.520 AC: 21533 AN: 41446

American (AMR) AF: 0.463 AC: 7073 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.486 AC: 1687 AN: 3468

East Asian (EAS) AF: 0.278 AC: 1433 AN: 5150

South Asian (SAS) AF: 0.525 AC: 2532 AN: 4820

European-Finnish (FIN) AF: 0.472 AC: 4992 AN: 10568

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.536 AC: 36427 AN: 67950

Other (OTH) AF: 0.506 AC: 1068 AN: 2110

Alfa AF: 0.532 Hom.: 10984

Bravo AF: 0.505

Asia WGS AF: 0.402 AC: 1399 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.24
DANN	Benign	0.54
PhyloP100		-4.9
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: rs4957028; hg19: chr5-361697;