rs6968865

Variant names:

• chr7-17247645-A-T
• rs6968865
• ENST00000642825.1:c.-284A>T

Variant summary

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

The ENST00000642825.1(AHR):​c.-284A>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.535 in 152,060 control chromosomes in the GnomAD database, including 22,852 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 0.53 (22849 hom., cov: 32)
  • Exomes 𝑓: 0.45 (3 hom.)
• Consequence: AHR ENST00000642825.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.347
• Publications: 38 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927609	XR_007060234.1	n.922+11607T>A		intron_variant	Intron 6 of 11
LOC101927609	XR_007060235.1	n.786+11607T>A		intron_variant	Intron 6 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000642825.1	c.-284A>T		5_prime_UTR_variant	Exon 3 of 15			ENSP00000495987.1
ENSG00000237773	ENST00000433005.2	n.649+11607T>A		intron_variant	Intron 3 of 5	2
ENSG00000237773	ENST00000643090.1	n.306+11607T>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81257 AN: 151920 Hom.: 22833 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.608

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.437

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.433

Gnomad FIN AF: 0.694

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.543

GnomAD4 exome AF: 0.455 AC: 10 AN: 22 Hom.: 3 Cov.: 0 AF XY: 0.800 AC XY: 8 AN XY: 10

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 9 AN: 18

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.535 AC: 81301 AN: 152038 Hom.: 22849 Cov.: 32 AF XY: 0.532 AC XY: 39507 AN XY: 74312

African (AFR) AF: 0.435 AC: 18027 AN: 41462

American (AMR) AF: 0.386 AC: 5900 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.437 AC: 1516 AN: 3468

East Asian (EAS) AF: 0.397 AC: 2050 AN: 5164

South Asian (SAS) AF: 0.432 AC: 2080 AN: 4818

European-Finnish (FIN) AF: 0.694 AC: 7326 AN: 10562

Middle Eastern (MID) AF: 0.503 AC: 148 AN: 294

European-Non Finnish (NFE) AF: 0.626 AC: 42557 AN: 67974

Other (OTH) AF: 0.544 AC: 1146 AN: 2106

Alfa AF: 0.597 Hom.: 15192

Bravo AF: 0.510

Asia WGS AF: 0.433 AC: 1505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.73
PhyloP100		0.35

Splicing

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

Other links and lift over

dbSNP: rs6968865; hg19: chr7-17287269;