dbSNP rs2672723: AHRR:c.352-14921A>G (chr5-398423-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.37

Publications

1 publications found

Variant links:

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]

AHRR links:

PDCD6-AHRR (HGNC:54724): (PDCD6-AHRR readthrough (NMD candidate)) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

PDCD6-AHRR links:

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new If you want to explore the variant's impact on the transcript NM_001377236.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001377236.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AHRR	NM_001377236.1	MANE Select	c.352-14921A>G	intron	N/A	NP_001364165.1	A0A7I2PK40
AHRR	NM_001377239.1		c.352-14921A>G	intron	N/A	NP_001364168.1	A0A7I2PK40
PDCD6-AHRR	NR_165159.2		n.645-14921A>G	intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AHRR	ENST00000684583.1	MANE Select	c.352-14921A>G	intron	N/A	ENSP00000507476.1	A0A7I2PK40
AHRR	ENST00000316418.10	TSL:1	c.352-14921A>G	intron	N/A	ENSP00000323816.6	A0A7I2PK40
PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*348-14921A>G	intron	N/A	ENSP00000424601.2	A0A6Q8PH81

Frequencies

GnomAD3 genomes

AF:

0.191

AC:

28948

AN:

151898

Hom.:

2990

Cov.:

show subpopulations

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.:

AF XY:

0.190

AC XY:

14116

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.226

AC:

9382

AN:

41444

American (AMR)

AF:

0.178

AC:

2725

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

474

AN:

3466

East Asian (EAS)

AF:

0.0300

AC:

155

AN:

5172

South Asian (SAS)

AF:

0.123

AC:

592

AN:

4812

European-Finnish (FIN)

AF:

0.199

AC:

2102

AN:

10580

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.188

AC:

12777

AN:

67948

Other (OTH)

AF:

0.199

AC:

421

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

1220

2440

3659

4879

6099

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

306

612

918

1224

1530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.34

(source)

DANN

Benign

0.64

PhyloP100

-3.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over