chr7-17296620-TTAAGG-T

Position:

• chr7-17296620-TTAAGG-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1 BP6_Moderate BS1 BS2

The ENST00000642825.1(AHR):​c.20+1_20+5delGTAAG variant causes a splice donor, splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 398,078 control chromosomes in the GnomAD database, including 11 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0069 (9 hom., cov: 32)
  • Exomes 𝑓: 0.00098 (2 hom.)
• Consequence: AHR ENST00000642825.1 splice_donor, splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.49

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 Likely_benign. Variant got -2 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
• BP6: Variant 7-17296620-TTAAGG-T is Benign according to our data. Variant chr7-17296620-TTAAGG-T is described in ClinVar as [Benign]. Clinvar id is 3341828.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00688 (1047/152284) while in subpopulation AFR AF= 0.0242 (1007/41560). AF 95% confidence interval is 0.023. There are 9 homozygotes in gnomad4. There are 514 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LOC101927609	XR_007060230.1	n.113-1352_113-1348delCCTTA		intron_variant
LOC101927609	XR_007060231.1	n.113-1352_113-1348delCCTTA		intron_variant
LOC101927609	XR_007060232.1	n.113-1352_113-1348delCCTTA		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AHR	ENST00000642825.1	c.20+1_20+5delGTAAG		splice_donor_variant, splice_region_variant, intron_variant				ENSP00000495987.1
ENSG00000237773	ENST00000654641.1	n.684_688delCCTTA		non_coding_transcript_exon_variant	1/3
ENSG00000237773	ENST00000665788.1	n.701_705delCCTTA		non_coding_transcript_exon_variant	1/2

Frequencies

GnomAD3 genomes AF: 0.00681 AC: 1036 AN: 152166 Hom.: 8 Cov.: 32

Gnomad AFR AF: 0.0240

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00164

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00382

GnomAD4 exome AF: 0.000980 AC: 241 AN: 245794 Hom.: 2 AF XY: 0.000771 AC XY: 96 AN XY: 124558

Gnomad4 AFR exome AF: 0.0253

Gnomad4 AMR exome AF: 0.00161

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000480

Gnomad4 NFE exome AF: 0.000101

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00688 AC: 1047 AN: 152284 Hom.: 9 Cov.: 32 AF XY: 0.00690 AC XY: 514 AN XY: 74474

Gnomad4 AFR AF: 0.0242

Gnomad4 AMR AF: 0.00163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00477 Hom.: 1

Bravo AF: 0.00767

Asia WGS AF: 0.00145 AC: 5 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

AHR: BS1, BS2; ENSG00000237773: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs146902850; hg19: chr7-17336244;