rs28521275

Positions:

• chr11-89295801-C-T

Variant summary

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

The 11-89295801-C-T variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 184,664 control chromosomes in the GnomAD database, including 29,478 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 0.58 (27049 hom., cov: 32)
  • Exomes 𝑓: 0.38 (2429 hom.)
• Consequence: TYR NM_000372.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.207

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYR	NM_000372.5			downstream_gene_variant		ENST00000263321.6
TYR	XM_011542970.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYR	ENST00000263321.6			downstream_gene_variant		1	NM_000372.5	P1

Frequencies

GnomAD3 genomes AF: 0.576 AC: 87479 AN: 151828 Hom.: 26996 Cov.: 32

Gnomad AFR AF: 0.819

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.524

GnomAD4 exome AF: 0.377 AC: 12343 AN: 32718 Hom.: 2429 Cov.: 0 AF XY: 0.376 AC XY: 6497 AN XY: 17286

Gnomad4 AFR exome AF: 0.684

Gnomad4 AMR exome AF: 0.451

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.345

Gnomad4 FIN exome AF: 0.395

Gnomad4 NFE exome AF: 0.369

Gnomad4 OTH exome AF: 0.393

GnomAD4 genome AF: 0.577 AC: 87603 AN: 151946 Hom.: 27049 Cov.: 32 AF XY: 0.576 AC XY: 42814 AN XY: 74274

Gnomad4 AFR AF: 0.820

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.527

Alfa AF: 0.543 Hom.: 2914

Bravo AF: 0.581

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	3.0
DANN	Benign	0.45

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs28521275; hg19: chr11-89028969;