chr7-17299271-A-T

Variant names:

• chr7-17299271-A-T
• NM_001621.5:c.7A>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001621.5(AHR):​c.7A>T​(p.Ser3Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,459,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 33)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: AHR NM_001621.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.990

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]

ENSG00000237773 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14759156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AHR	NM_001621.5	c.7A>T	p.Ser3Cys	missense_variant	Exon 1 of 11	ENST00000242057.9	NP_001612.1
LOC101927609	XR_007060234.1	n.50T>A		non_coding_transcript_exon_variant	Exon 1 of 12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000242057.9	c.7A>T	p.Ser3Cys	missense_variant	Exon 1 of 11	1	NM_001621.5	ENSP00000242057.4
ENSG00000283321	ENST00000637807.1	c.-24A>T		upstream_gene_variant		5		ENSP00000490530.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1459878 Hom.: 0 Cov.: 31 AF XY: 0.00000551 AC XY: 4 AN XY: 726328

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: 0.00000450

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.15	N
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.55	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.035
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.016	D
Polyphen		0.77	P
Vest4		0.15
MutPred		0.34		Gain of catalytic residue at M1 (P = 0.0029);
MVP		0.19
MPC		0.28
ClinPred		0.73	D
GERP RS		0.45
Varity_R		0.21
gMVP		0.67

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: chr7-17338895;