rs3793976

Positions:

• chr11-89185899-C-A

Variant summary

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

The NM_000372.5(TYR):​c.820-5303C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,036 control chromosomes in the GnomAD database, including 4,763 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 0.21 (4763 hom., cov: 32)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.429 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYR	NM_000372.5	c.820-5303C>A		intron_variant		ENST00000263321.6
TYR	XM_011542970.3	c.820-5303C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYR	ENST00000263321.6	c.820-5303C>A		intron_variant		1	NM_000372.5	P1
TYR	ENST00000526139.1	n.881-5303C>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31301 AN: 151920 Hom.: 4734 Cov.: 32

Gnomad AFR AF: 0.434

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.206 AC: 31389 AN: 152036 Hom.: 4763 Cov.: 32 AF XY: 0.206 AC XY: 15331 AN XY: 74316

Gnomad4 AFR AF: 0.434

Gnomad4 AMR AF: 0.160

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.100

Gnomad4 OTH AF: 0.210

Alfa AF: 0.162 Hom.: 453

Bravo AF: 0.216

Asia WGS AF: 0.183 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.88
DANN	Benign	0.33

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: rs3793976; hg19: chr11-88919067;