rs12295166

Positions:

• chr11-89242989-T-C

Variant summary

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

The NM_000372.5(TYR):​c.1184+15019T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 152,202 control chromosomes in the GnomAD database, including 6,413 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 0.25 (6413 hom., cov: 33)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.31

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYR	NM_000372.5	c.1184+15019T>C		intron_variant		ENST00000263321.6	NP_000363.1
TYR	XM_011542970.3	c.1184+15019T>C		intron_variant			XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6	c.1184+15019T>C		intron_variant		1	NM_000372.5	ENSP00000263321	P1

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37881 AN: 152084 Hom.: 6413 Cov.: 33

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.313

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

GnomAD4 genome AF: 0.249 AC: 37867 AN: 152202 Hom.: 6413 Cov.: 33 AF XY: 0.238 AC XY: 17685 AN XY: 74410

Gnomad4 AFR AF: 0.0687

Gnomad4 AMR AF: 0.277

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.00232

Gnomad4 SAS AF: 0.103

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.376

Gnomad4 OTH AF: 0.310

Alfa AF: 0.284 Hom.: 922

Bravo AF: 0.253

Asia WGS AF: 0.0530 AC: 187 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.26
DANN	Benign	0.45

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: rs12295166; hg19: chr11-88976157;