chr11-89236606-T-C

Position:

• chr11-89236606-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+8636T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.314 in 152,080 control chromosomes in the GnomAD database, including 8,165 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 0.31 (8165 hom., cov: 32)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.926

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYR	NM_000372.5	c.1184+8636T>C		intron_variant		ENST00000263321.6	NP_000363.1
TYR	XM_011542970.3	c.1184+8636T>C		intron_variant			XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6	c.1184+8636T>C		intron_variant		1	NM_000372.5	ENSP00000263321	P1

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47778 AN: 151962 Hom.: 8151 Cov.: 32

Gnomad AFR AF: 0.450

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.240

Gnomad ASJ AF: 0.267

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.287

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.314 AC: 47825 AN: 152080 Hom.: 8165 Cov.: 32 AF XY: 0.309 AC XY: 22952 AN XY: 74354

Gnomad4 AFR AF: 0.450

Gnomad4 AMR AF: 0.240

Gnomad4 ASJ AF: 0.267

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.287

Gnomad4 OTH AF: 0.286

Alfa AF: 0.280 Hom.: 12683

Bravo AF: 0.321

Asia WGS AF: 0.161 AC: 559 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.64
DANN	Benign	0.52

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: rs10765198; hg19: chr11-88969774;