Genetic Variant NM_001377236.1:c.62+139C>T (chr5-344103-C-T) – 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.62+139C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 859,742 control chromosomes in the GnomAD database, including 135,475 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 ( 23442 hom., cov: 27)

Exomes 𝑓: 0.56 ( 112033 hom. )

Consequence

AHRR
NM_001377236.1 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0490

Publications

7 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=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
AHRR	NM_001377236.1 link	c.62+139C>T	intron_variant	Intron 2 of 10	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1 link	c.62+139C>T	intron_variant	Intron 2 of 10		NP_001364168.1
PDCD6-AHRR	NR_165159.2 link	n.355+139C>T	intron_variant	Intron 4 of 13
PDCD6-AHRR	NR_165163.2 link	n.355+139C>T	intron_variant	Intron 4 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1 link	c.62+139C>T		intron_variant	Intron 2 of 10		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1 link	n.*58+139C>T		intron_variant	Intron 4 of 13			ENSP00000502570.1

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

83378

AN:

150790

Hom.:

23428

Cov.:

show subpopulations

Gnomad AFR

AF:

0.622

Gnomad AMI

AF:

0.453

Gnomad AMR

AF:

0.500

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.288

Gnomad SAS

AF:

0.532

Gnomad FIN

AF:

0.487

Gnomad MID

AF:

0.570

Gnomad NFE

AF:

0.554

Gnomad OTH

AF:

0.554

GnomAD4 exome

AF:

0.559

AC:

396276

AN:

708844

Hom.:

112033

AF XY:

0.558

AC XY:

205510

AN XY:

368540

show subpopulations

African (AFR)

AF:

0.637

AC:

8342

AN:

13106

American (AMR)

AF:

0.476

AC:

5785

AN:

12144

Ashkenazi Jewish (ASJ)

AF:

0.586

AC:

10084

AN:

17214

East Asian (EAS)

AF:

0.379

AC:

9253

AN:

24442

South Asian (SAS)

AF:

0.551

AC:

30446

AN:

55296

European-Finnish (FIN)

AF:

0.502

AC:

16840

AN:

33558

Middle Eastern (MID)

AF:

0.591

AC:

1705

AN:

2886

European-Non Finnish (NFE)

AF:

0.571

AC:

295121

AN:

516432

Other (OTH)

AF:

0.554

AC:

18700

AN:

33766

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

8506

17011

25517

34022

42528

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5850

11700

17550

23400

29250

<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:

0.553

AC:

83438

AN:

150898

Hom.:

23442

Cov.:

AF XY:

0.548

AC XY:

40394

AN XY:

73646

show subpopulations

African (AFR)

AF:

0.621

AC:

25563

AN:

41142

American (AMR)

AF:

0.500

AC:

7619

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.571

AC:

1974

AN:

3460

East Asian (EAS)

AF:

0.289

AC:

1409

AN:

4878

South Asian (SAS)

AF:

0.532

AC:

2543

AN:

4784

European-Finnish (FIN)

AF:

0.487

AC:

5087

AN:

10448

Middle Eastern (MID)

AF:

0.562

AC:

164

AN:

292

European-Non Finnish (NFE)

AF:

0.554

AC:

37502

AN:

67660

Other (OTH)

AF:

0.557

AC:

1168

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

1817

3633

5450

7266

9083

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.547

Hom.:

2875

Bravo

AF:

0.554

Asia WGS

AF:

0.420

AC:

1457

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.3

(source)

DANN

Benign

0.83

PhyloP100

-0.049

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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