rs17793678

Positions:

• chr11-89188356-C-T

Variant summary

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

The NM_000372.5(TYR):​c.820-2846C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,830 control chromosomes in the GnomAD database, including 4,271 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 0.23 (4271 hom., cov: 31)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259

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=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.279 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYR	NM_000372.5	c.820-2846C>T		intron_variant		ENST00000263321.6
TYR	XM_011542970.3	c.820-2846C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYR	ENST00000263321.6	c.820-2846C>T		intron_variant		1	NM_000372.5	P1
TYR	ENST00000526139.1	n.881-2846C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34810 AN: 151712 Hom.: 4269 Cov.: 31

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.210

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.109

Gnomad FIN AF: 0.253

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.226

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

GnomAD4 genome AF: 0.229 AC: 34819 AN: 151830 Hom.: 4271 Cov.: 31 AF XY: 0.226 AC XY: 16746 AN XY: 74148

Gnomad4 AFR AF: 0.162

Gnomad4 AMR AF: 0.210

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.178

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.253

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.223

Alfa AF: 0.267 Hom.: 970

Bravo AF: 0.225

Asia WGS AF: 0.140 AC: 486 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.77

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: rs17793678; hg19: chr11-88921524;