5-434607-G-T

Variant names:

• chr5-434607-G-T
• NM_001377236.1:c.1867G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001377236.1(AHRR):​c.1867G>T​(p.Asp623Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,412,898 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: AHRR NM_001377236.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057283938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHRR	NM_001377236.1	c.1867G>T	p.Asp623Tyr	missense_variant	Exon 11 of 11	ENST00000684583.1	NP_001364165.1
AHRR	NM_001377239.1	c.1867G>T	p.Asp623Tyr	missense_variant	Exon 11 of 11		NP_001364168.1
PDCD6-AHRR	NR_165159.2	n.2214G>T		non_coding_transcript_exon_variant	Exon 14 of 14
PDCD6-AHRR	NR_165163.2	n.2160G>T		non_coding_transcript_exon_variant	Exon 13 of 13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHRR	ENST00000684583.1	c.1867G>T	p.Asp623Tyr	missense_variant	Exon 11 of 11		NM_001377236.1	ENSP00000507476.1
PDCD6-AHRR	ENST00000675395.1	n.*1917G>T		non_coding_transcript_exon_variant	Exon 14 of 14			ENSP00000502570.1
PDCD6-AHRR	ENST00000675395.1	n.*1917G>T		3_prime_UTR_variant	Exon 14 of 14			ENSP00000502570.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1412898 Hom.: 0 Cov.: 100 AF XY: 0.00000429 AC XY: 3 AN XY: 698538

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000368

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	5.8
DANN	Benign	0.40
DEOGEN2	Benign	0.050	T;.;T;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.077	N
LIST_S2	Benign	0.51	T;T;T;T
M_CAP	Benign	0.0014	T
MetaRNN	Benign	0.057	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.0	N;.;.;.
PrimateAI	Benign	0.44	T
PROVEAN	Benign	1.1	N;N;N;N
REVEL	Benign	0.029
Sift	Benign	0.20	T;T;T;T
Sift4G	Benign	1.0	.;.;T;T
Polyphen		0.0	B;B;.;B
Vest4		0.17
MutPred		0.34		Gain of phosphorylation at D627 (P = 0.0152);.;.;.;
MVP		0.27
MPC		0.10
ClinPred		0.046	T
GERP RS		3.3
Varity_R		0.054
gMVP		0.23

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-434722;