7-17296411-T-C

Variant names:

• chr7-17296411-T-C
• rs3757824
• ENST00000642825.1:c.-114+26T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000642825.1(AHR):​c.-114+26T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 384,698 control chromosomes in the GnomAD database, including 9,789 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.21 (3557 hom., cov: 31)
  • Exomes 𝑓: 0.22 (6232 hom.)
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34
• Publications: 8 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000642825.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AHR	ENST00000642825.1		c.-114+26T>C		intron	N/A	ENSP00000495987.1	A0A2R8Y7G1
	ENSG00000237773	ENST00000654641.1		n.898A>G		non_coding_transcript_exon	Exon 1 of 3
	ENSG00000237773	ENST00000665788.1		n.915A>G		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31631 AN: 151676 Hom.: 3548 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.149

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.221

GnomAD4 exome AF: 0.222 AC: 51683 AN: 232904 Hom.: 6232 Cov.: 0 AF XY: 0.222 AC XY: 26242 AN XY: 118182

African (AFR) AF: 0.172 AC: 1195 AN: 6930

American (AMR) AF: 0.367 AC: 2618 AN: 7136

Ashkenazi Jewish (ASJ) AF: 0.156 AC: 1382 AN: 8880

East Asian (EAS) AF: 0.344 AC: 7605 AN: 22094

South Asian (SAS) AF: 0.289 AC: 601 AN: 2080

European-Finnish (FIN) AF: 0.158 AC: 3013 AN: 19082

Middle Eastern (MID) AF: 0.188 AC: 230 AN: 1224

European-Non Finnish (NFE) AF: 0.210 AC: 31519 AN: 149872

Other (OTH) AF: 0.226 AC: 3520 AN: 15606

GnomAD4 genome AF: 0.209 AC: 31650 AN: 151794 Hom.: 3557 Cov.: 31 AF XY: 0.209 AC XY: 15544 AN XY: 74202

African (AFR) AF: 0.174 AC: 7212 AN: 41368

American (AMR) AF: 0.308 AC: 4694 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3466

East Asian (EAS) AF: 0.270 AC: 1394 AN: 5170

South Asian (SAS) AF: 0.276 AC: 1333 AN: 4822

European-Finnish (FIN) AF: 0.157 AC: 1643 AN: 10498

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14159 AN: 67904

Other (OTH) AF: 0.219 AC: 462 AN: 2108

Alfa AF: 0.212 Hom.: 13740

Bravo AF: 0.220

Asia WGS AF: 0.249 AC: 864 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.028
DANN	Benign	0.57
PhyloP100		-2.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3757824;

hg19: chr7-17336035;