rs7483056

Positions:

• chr11-2169289-A-G
• chr11-2169289-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000360.4(TH):​c.312+361T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 151,888 control chromosomes in the GnomAD database, including 17,157 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 0.47 (17157 hom., cov: 32)
• Consequence: TH NM_000360.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

Genes affected

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TH	NM_000360.4	c.312+361T>C		intron_variant		ENST00000352909.8
TH	NM_199292.3	c.405+361T>C		intron_variant
TH	NM_199293.3	c.393+361T>C		intron_variant
TH	XM_011520335.3	c.324+361T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TH	ENST00000352909.8	c.312+361T>C		intron_variant		1	NM_000360.4	P1

Frequencies

GnomAD3 genomes AF: 0.474 AC: 71901 AN: 151772 Hom.: 17133 Cov.: 32

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.489

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.473

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.509

Gnomad MID AF: 0.452

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.482

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

GnomAD4 genome AF: 0.474 AC: 71970 AN: 151888 Hom.: 17157 Cov.: 32 AF XY: 0.477 AC XY: 35417 AN XY: 74216

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.473

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.509

Gnomad4 NFE AF: 0.455

Gnomad4 OTH AF: 0.482

Alfa AF: 0.456 Hom.: 13646

Bravo AF: 0.477

Asia WGS AF: 0.454 AC: 1575 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.31
DANN	Benign	0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs7483056; hg19: chr11-2190519; COSMIC: COSV60767560; COSMIC: COSV60767560;