rs530894063

Variant names:

• chr7-17299328-A-C
• rs530894063
• NM_001621.5:c.64A>C

Your query was ambiguous. Multiple possible variants found:

• chr7-17299328-A-C
• chr7-17299328-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001621.5(AHR):​c.64A>C​(p.Thr22Pro) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000657 in 152,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
• Consequence: AHR NM_001621.5 missense, splice_region
• Scores: Splicing: ADA: 0.9903
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.70

Genes affected

AHR (HGNC:348): (aryl hydrocarbon receptor) The protein encoded by this gene is a ligand-activated helix-loop-helix transcription factor involved in the regulation of biological responses to planar aromatic hydrocarbons. This receptor has been shown to regulate xenobiotic-metabolizing enzymes such as cytochrome P450. Before ligand binding, the encoded protein is sequestered in the cytoplasm; upon ligand binding, this protein moves to the nucleus and stimulates transcription of target genes. [provided by RefSeq, Sep 2015]

ENSG00000283321 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.64A>C	p.Thr22Pro	missense_variant, splice_region_variant	Exon 1 of 11	ENST00000242057.9	NP_001612.1
LOC101927609	XR_007060234.1	n.-8T>G		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.64A>C	p.Thr22Pro	missense_variant, splice_region_variant	Exon 1 of 11	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.34A>C	p.Thr12Pro	missense_variant, splice_region_variant	Exon 1 of 12	5		ENSP00000490530.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152200 Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1 AN XY: 74352

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;.
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.78	.;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.8	L;.
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-2.4	N;.
REVEL	Benign	0.077
Sift	Benign	0.043	D;.
Sift4G	Benign	0.082	T;.
Polyphen		0.73	P;.
Vest4		0.18
MutPred		0.24		Loss of phosphorylation at T22 (P = 0.0335);.;
MVP		0.38
MPC		0.31
ClinPred		0.91	D
GERP RS		4.8
Varity_R		0.59
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	0.99
dbscSNV1_RF	Pathogenic	0.86
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

Other links and lift over

dbSNP: rs530894063; hg19: chr7-17338952;