rs763621

Variant names:

• chr7-17259700-T-C
• rs763621
• ENST00000642825.1:c.-203+11974T>C

Variant summary

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

The ENST00000642825.1(AHR):​c.-203+11974T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0601 in 152,088 control chromosomes in the GnomAD database, including 837 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 0.060 (837 hom., cov: 32)
• Consequence: AHR ENST00000642825.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC101927609	XR_007060234.1	n.846-372A>G		intron_variant	Intron 5 of 11
LOC101927609	XR_007060235.1	n.710-372A>G		intron_variant	Intron 5 of 6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000642825.1	c.-203+11974T>C		intron_variant	Intron 3 of 14			ENSP00000495987.1
ENSG00000237773	ENST00000433005.2	n.573-372A>G		intron_variant	Intron 2 of 5	2
ENSG00000237773	ENST00000452249.7	n.537-372A>G		intron_variant	Intron 3 of 4	3

Frequencies

GnomAD3 genomes AF: 0.0600 AC: 9114 AN: 151970 Hom.: 832 Cov.: 32

Gnomad AFR AF: 0.204

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0227

Gnomad ASJ AF: 0.00894

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.00276

Gnomad OTH AF: 0.0465

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0601 AC: 9140 AN: 152088 Hom.: 837 Cov.: 32 AF XY: 0.0586 AC XY: 4359 AN XY: 74360

African (AFR) AF: 0.204 AC: 8443 AN: 41438

American (AMR) AF: 0.0226 AC: 346 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00894 AC: 31 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.00277 AC: 188 AN: 67988

Other (OTH) AF: 0.0460 AC: 97 AN: 2108

Alfa AF: 0.0370 Hom.: 70

Bravo AF: 0.0693

Asia WGS AF: 0.0140 AC: 48 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.83
DANN	Benign	0.67
PhyloP100		-0.40

Splicing

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

Other links and lift over

dbSNP: rs763621; hg19: chr7-17299324;