dbSNP rs12188164: AHRR:c.908+115C>A (chr5-428121-C-A) – 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.908+115C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,225,110 control chromosomes in the GnomAD database, including 82,016 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 0.26 ( 6894 hom., cov: 34)

Exomes 𝑓: 0.36 ( 75122 hom. )

Consequence

AHRR
NM_001377236.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.387

Publications

37 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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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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AHRR	NM_001377236.1 link	c.908+115C>A	intron_variant	Intron 8 of 10	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1 link	c.908+115C>A	intron_variant	Intron 8 of 10		NP_001364168.1
PDCD6-AHRR	NR_165159.2 link	n.1255+115C>A	intron_variant	Intron 11 of 13
PDCD6-AHRR	NR_165163.2 link	n.1201+115C>A	intron_variant	Intron 10 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1 link	c.908+115C>A		intron_variant	Intron 8 of 10		NM_001377236.1	ENSP00000507476.1		A0A7I2PK40
PDCD6-AHRR	ENST00000675395.1 link	n.*958+115C>A		intron_variant	Intron 11 of 13			ENSP00000502570.1		A0A6Q8PH81

Frequencies

GnomAD3 genomes

AF:

0.264

AC:

40128

AN:

152004

Hom.:

6894

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0701

Gnomad AMI

AF:

0.476

Gnomad AMR

AF:

0.245

Gnomad ASJ

AF:

0.246

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.223

Gnomad FIN

AF:

0.394

Gnomad MID

AF:

0.114

Gnomad NFE

AF:

0.388

Gnomad OTH

AF:

0.259

GnomAD4 exome

AF:

0.358

AC:

384580

AN:

1072988

Hom.:

75122

AF XY:

0.355

AC XY:

189875

AN XY:

535012

show subpopulations

African (AFR)

AF:

0.0541

AC:

1315

AN:

24310

American (AMR)

AF:

0.267

AC:

7964

AN:

29870

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

5106

AN:

21128

East Asian (EAS)

AF:

0.00147

AC:

AN:

33918

South Asian (SAS)

AF:

0.239

AC:

16090

AN:

67438

European-Finnish (FIN)

AF:

0.397

AC:

18524

AN:

46658

Middle Eastern (MID)

AF:

0.168

AC:

636

AN:

3790

European-Non Finnish (NFE)

AF:

0.400

AC:

319876

AN:

799198

Other (OTH)

AF:

0.322

AC:

15019

AN:

46678

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11916

23832

35747

47663

59579

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8922

17844

26766

35688

44610

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.264

AC:

40131

AN:

152122

Hom.:

6894

Cov.:

AF XY:

0.260

AC XY:

19354

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0699

AC:

2906

AN:

41566

American (AMR)

AF:

0.245

AC:

3741

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.246

AC:

852

AN:

3468

East Asian (EAS)

AF:

0.00520

AC:

AN:

5192

South Asian (SAS)

AF:

0.225

AC:

1085

AN:

4822

European-Finnish (FIN)

AF:

0.394

AC:

4147

AN:

10532

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.388

AC:

26362

AN:

67948

Other (OTH)

AF:

0.258

AC:

544

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1431

2863

4294

5726

7157

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.332

Hom.:

33388

Bravo

AF:

0.244

Asia WGS

AF:

0.0990

AC:

343

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.93

(source)

DANN

Benign

0.52

PhyloP100

-0.39

PromoterAI

-0.045

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over