11-2163897-C-G

Position:

• chr11-2163897-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The variant allele was found at a frequency of 0.0605 in 209,268 control chromosomes in the GnomAD database, including 1,606 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.078 (1505 hom., cov: 33)
  • Exomes 𝑓: 0.014 (101 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.459

Genes affected

(HGNC:):

TH (HGNC:11782): (tyrosine hydroxylase) The protein encoded by this gene is involved in the conversion of tyrosine to dopamine. It is the rate-limiting enzyme in the synthesis of catecholamines, hence plays a key role in the physiology of adrenergic neurons. Mutations in this gene have been associated with autosomal recessive Segawa syndrome. Alternatively spliced transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 11-2163897-C-G is Benign according to our data. Variant chr11-2163897-C-G is described in ClinVar as [Benign]. Clinvar id is 1274135.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TH	NM_000360.4	c.*336G>C		downstream_gene_variant		ENST00000352909.8	NP_000351.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TH	ENST00000352909.8	c.*336G>C		downstream_gene_variant		1	NM_000360.4	ENSP00000325951.4
TH	ENST00000381178.5	c.*336G>C		downstream_gene_variant		1		ENSP00000370571.1
TH	ENST00000381175.5	c.*336G>C		downstream_gene_variant		1		ENSP00000370567.1
TH	ENST00000333684.9	c.*336G>C		downstream_gene_variant		1		ENSP00000328814.6

Frequencies

GnomAD3 genomes AF: 0.0779 AC: 11841 AN: 152090 Hom.: 1494 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0348

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00149

Gnomad OTH AF: 0.0549

GnomAD4 exome AF: 0.0137 AC: 779 AN: 57060 Hom.: 101 Cov.: 0 AF XY: 0.0122 AC XY: 351 AN XY: 28656

Gnomad4 AFR exome AF: 0.269

Gnomad4 AMR exome AF: 0.0232

Gnomad4 ASJ exome AF: 0.00491

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00120

Gnomad4 OTH exome AF: 0.0246

GnomAD4 genome AF: 0.0780 AC: 11873 AN: 152208 Hom.: 1505 Cov.: 33 AF XY: 0.0751 AC XY: 5589 AN XY: 74424

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0348

Gnomad4 ASJ AF: 0.00548

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00147

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0610 Hom.: 126

Bravo AF: 0.0900

Asia WGS AF: 0.0120 AC: 44 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.49

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3842726; hg19: chr11-2185127;