7-17299272-G-C

Variant names:

• chr7-17299272-G-C
• rs1278062693
• NM_001621.5:c.8G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001621.5(AHR):​c.8G>C​(p.Ser3Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S3G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AHR NM_001621.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.337
• Publications: 0 publications found

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]

AHR Gene-Disease associations (from GenCC):

• retinitis pigmentosa 85

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• foveal hypoplasia

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ENSG00000237773 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.067427576).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001621.5. 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
	AHR	NM_001621.5	MANE Select	c.8G>C	p.Ser3Thr	missense	Exon 1 of 11	NP_001612.1	P35869

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	ENST00000242057.9	TSL:1 MANE Select	c.8G>C	p.Ser3Thr	missense	Exon 1 of 11	ENSP00000242057.4	P35869
	AHR	ENST00000463496.1	TSL:1	n.8G>C		non_coding_transcript_exon	Exon 1 of 12	ENSP00000436466.1	P35869
	AHR	ENST00000964518.1		c.8G>C	p.Ser3Thr	missense	Exon 1 of 11	ENSP00000634577.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.54
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.078	D
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.55	N
PhyloP100		0.34
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.027
Sift	Benign	0.045	D
Sift4G	Benign	0.17	T
Polyphen		0.0	B
Vest4		0.12
MutPred		0.17		Loss of phosphorylation at S3 (P = 0.0431)
MVP		0.15
MPC		0.10
ClinPred		0.15	T
GERP RS		1.7
PromoterAI		0.033	Neutral
Varity_R		0.069
gMVP		0.53
Mutation Taster		=98/2	polymorphism

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: rs1278062693; hg19: chr7-17338896;