dbSNP rs1799989: TYR:c.-199C>A (chr11-89177755-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000372.5(TYR):c.-199C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.138 in 614,940 control chromosomes in the GnomAD database, including 6,858 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2448 hom., cov: 32)

Exomes 𝑓: 0.13 ( 4410 hom. )

Consequence

TYR
NM_000372.5 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3O:1

Conservation

PhyloP100: -0.278

Variant links:

Genes affected

TYR (HGNC:12442): (tyrosinase) The enzyme encoded by this gene catalyzes the first 2 steps, and at least 1 subsequent step, in the conversion of tyrosine to melanin. The enzyme has both tyrosine hydroxylase and dopa oxidase catalytic activities, and requires copper for function. Mutations in this gene result in oculocutaneous albinism, and nonpathologic polymorphisms result in skin pigmentation variation. The human genome contains a pseudogene similar to the 3' half of this gene. [provided by RefSeq, Oct 2008]

TYR links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYR	NM_000372.5 link	c.-199C>A		upstream_gene_variant		ENST00000263321.6	NP_000363.1	P14679-1L8B082
TYR	XM_011542970.3 link	c.-199C>A		upstream_gene_variant			XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6 link	c.-199C>A		upstream_gene_variant		1	NM_000372.5	ENSP00000263321.4		P14679-1
TYR	ENST00000526139.1 link	n.-138C>A		upstream_gene_variant		1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24948

AN:

151944

Hom.:

2430

Cov.:

show subpopulations

Gnomad AFR

AF:

0.274

Gnomad AMI

AF:

0.0724

Gnomad AMR

AF:

0.140

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.119

Gnomad SAS

AF:

0.200

Gnomad FIN

AF:

0.174

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.171

GnomAD4 exome

AF:

0.130

AC:

59995

AN:

462876

Hom.:

4410

Cov.:

AF XY:

0.134

AC XY:

32686

AN XY:

244832

show subpopulations

Gnomad4 AFR exome

AF:

0.273

Gnomad4 AMR exome

AF:

0.132

Gnomad4 ASJ exome

AF:

0.116

Gnomad4 EAS exome

AF:

0.141

Gnomad4 SAS exome

AF:

0.205

Gnomad4 FIN exome

AF:

0.164

Gnomad4 NFE exome

AF:

0.105

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.164

AC:

25008

AN:

152064

Hom.:

2448

Cov.:

AF XY:

0.167

AC XY:

12415

AN XY:

74342

show subpopulations

Gnomad4 AFR

AF:

0.275

Gnomad4 AMR

AF:

0.140

Gnomad4 ASJ

AF:

0.118

Gnomad4 EAS

AF:

0.119

Gnomad4 SAS

AF:

0.201

Gnomad4 FIN

AF:

0.174

Gnomad4 NFE

AF:

0.105

Gnomad4 OTH

AF:

0.176

Alfa

AF:

0.0831

Hom.:

140

Bravo

AF:

0.166

ClinVar

Significance: Benign

Submissions summary: Benign:3Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Retina International

Significance: not provided

Review Status: no classification provided

Collection Method: literature only

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oculocutaneous albinism type 1A

Benign:1

Jan 01, 1993

OMIM

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

4.8

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over