rs1847134

Positions:

• chr11-89272085-A-C

Variant summary

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

The NM_000372.5(TYR):​c.1185-12688A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 151,752 control chromosomes in the GnomAD database, including 5,428 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 0.26 (5428 hom., cov: 32)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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 (NFE) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYR	NM_000372.5	c.1185-12688A>C		intron_variant		ENST00000263321.6
TYR	XM_011542970.3	c.1185-12688A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYR	ENST00000263321.6	c.1185-12688A>C		intron_variant		1	NM_000372.5	P1

Frequencies

GnomAD3 genomes AF: 0.261 AC: 39603 AN: 151634 Hom.: 5425 Cov.: 32

Gnomad AFR AF: 0.202

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.228

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.169

Gnomad SAS AF: 0.122

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.244

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

GnomAD4 genome AF: 0.261 AC: 39616 AN: 151752 Hom.: 5428 Cov.: 32 AF XY: 0.258 AC XY: 19106 AN XY: 74144

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.271

Gnomad4 EAS AF: 0.169

Gnomad4 SAS AF: 0.122

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.313

Gnomad4 OTH AF: 0.241

Alfa AF: 0.293 Hom.: 6445

Bravo AF: 0.254

Asia WGS AF: 0.141 AC: 492 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	2.7
DANN	Benign	0.69

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: rs1847134; hg19: chr11-89005253; COSMIC: COSV54484926;