5-422791-C-T

Variant names:

• chr5-422791-C-T
• rs61755969
• NM_001377236.1:c.504C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001377236.1(AHRR):​c.504C>T​(p.Cys168Cys) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.180
• Publications: 1 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	NM_001377236.1	MANE Select	c.504C>T	p.Cys168Cys	synonymous	Exon 6 of 11	NP_001364165.1	A0A7I2PK40
	AHRR	NM_001377239.1		c.504C>T	p.Cys168Cys	synonymous	Exon 6 of 11	NP_001364168.1	A0A7I2PK40
	PDCD6-AHRR	NR_165159.2		n.797C>T		non_coding_transcript_exon	Exon 8 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHRR	ENST00000684583.1	MANE Select	c.504C>T	p.Cys168Cys	synonymous	Exon 6 of 11	ENSP00000507476.1	A0A7I2PK40
	AHRR	ENST00000316418.10	TSL:1	c.504C>T	p.Cys168Cys	synonymous	Exon 6 of 11	ENSP00000323816.6	A0A7I2PK40
	PDCD6-AHRR	ENST00000505113.6	TSL:1	n.*500C>T		non_coding_transcript_exon	Exon 8 of 13	ENSP00000424601.2	A0A6Q8PH81

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2270 AN: 152186 Hom.: 38 Cov.: 32

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

GnomAD2 exomes AF: 0.00753 AC: 1879 AN: 249434 AF XY: 0.00747

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 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.: 90 Cov.: 30 AF XY: 0.00714 AC XY: 5194 AN XY: 727212

African (AFR) AF: 0.0431 AC: 1442 AN: 33480

American (AMR) AF: 0.00389 AC: 174 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26134

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.0137 AC: 1181 AN: 86252

European-Finnish (FIN) AF: 0.000899 AC: 48 AN: 53394

Middle Eastern (MID) AF: 0.00641 AC: 37 AN: 5768

European-Non Finnish (NFE) AF: 0.00643 AC: 7152 AN: 1111988

Other (OTH) AF: 0.00685 AC: 414 AN: 60394

GnomAD4 genome AF: 0.0149 AC: 2271 AN: 152304 Hom.: 36 Cov.: 32 AF XY: 0.0143 AC XY: 1066 AN XY: 74474

African (AFR) AF: 0.0407 AC: 1693 AN: 41558

American (AMR) AF: 0.00581 AC: 89 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0122 AC: 59 AN: 4820

European-Finnish (FIN) AF: 0.000753 AC: 8 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00591 AC: 402 AN: 68020

Other (OTH) AF: 0.00851 AC: 18 AN: 2116

Alfa AF: 0.00969 Hom.: 9

Bravo AF: 0.0175

Asia WGS AF: 0.0120 AC: 43 AN: 3478

EpiCase AF: 0.00589

EpiControl AF: 0.00581

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	11
DANN	Benign	0.83
PhyloP100		0.18
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: rs61755969; hg19: chr5-422906;