Variant chr5-422791-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001377236.1(AHRR):c.504C>T(p.Cys168=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00789 in 1,614,134 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 36 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 90 hom. )

Consequence

AHRR
NM_001377236.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.180

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:):

PDCD6-AHRR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 5-422791-C-T is Benign according to our data. Variant chr5-422791-C-T is described in ClinVar as [Benign]. Clinvar id is 778862.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.18 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0149 (2271/152304) while in subpopulation AFR AF= 0.0407 (1693/41558). AF 95% confidence interval is 0.0391. There are 36 homozygotes in gnomad4. There are 1066 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
AHRR	NM_001377236.1 linkuse as main transcript	c.504C>T	p.Cys168=	synonymous_variant	6/11	ENST00000684583.1
PDCD6-AHRR	NR_165159.2 linkuse as main transcript	n.797C>T		non_coding_transcript_exon_variant	8/14
AHRR	NM_001377239.1 linkuse as main transcript	c.504C>T	p.Cys168=	synonymous_variant	6/11
PDCD6-AHRR	NR_165163.2 linkuse as main transcript	n.797C>T		non_coding_transcript_exon_variant	8/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AHRR	ENST00000684583.1 linkuse as main transcript	c.504C>T	p.Cys168=	synonymous_variant	6/11		NM_001377236.1	P1

Frequencies

GnomAD3 genomes

AF:

0.0149

AC:

2270

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00582

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0122

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00591

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00753

AC:

1879

AN:

249434

Hom.:

AF XY:

0.00747

AC XY:

1011

AN XY:

135366

show subpopulations

Gnomad AFR exome

AF:

0.0447

Gnomad AMR exome

AF:

0.00356

Gnomad ASJ exome

AF:

0.000397

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.000742

Gnomad NFE exome

AF:

0.00551

Gnomad OTH exome

AF:

0.00578

GnomAD4 exome

AF:

0.00716

AC:

10465

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00714

AC XY:

5194

AN XY:

727212

show subpopulations

Gnomad4 AFR exome

AF:

0.0431

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.000536

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0137

Gnomad4 FIN exome

AF:

0.000899

Gnomad4 NFE exome

AF:

0.00643

Gnomad4 OTH exome

AF:

0.00685

GnomAD4 genome

AF:

0.0149

AC:

2271

AN:

152304

Hom.:

Cov.:

AF XY:

0.0143

AC XY:

1066

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0407

Gnomad4 AMR

AF:

0.00581

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0122

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00591

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00946

Hom.:

Bravo

AF:

0.0175

Asia WGS

AF:

0.0120

AC:

AN:

3478

EpiCase

AF:

0.00589

EpiControl

AF:

0.00581

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 12, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.83

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over