rs11018528

Variant names:

• chr11-89197209-A-G
• rs11018528
• NM_000372.5:c.1036+5791A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000372.5(TYR):​c.1036+5791A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 152,020 control chromosomes in the GnomAD database, including 4,818 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 (4818 hom., cov: 32)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0210
• Publications: 18 publications found

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]

TYR Gene-Disease associations (from GenCC):

• oculocutaneous albinism type 1

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• oculocutaneous albinism type 1A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine
• Waardenburg syndrome type 2

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• minimal pigment oculocutaneous albinism type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• oculocutaneous albinism type 1B

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• temperature-sensitive oculocutaneous albinism type 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYR	NM_000372.5	c.1036+5791A>G		intron_variant	Intron 2 of 4	ENST00000263321.6	NP_000363.1
TYR	XM_011542970.3	c.1036+5791A>G		intron_variant	Intron 2 of 5		XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6	c.1036+5791A>G		intron_variant	Intron 2 of 4	1	NM_000372.5	ENSP00000263321.4
TYR	ENST00000526139.1	n.1098-3054A>G		intron_variant	Intron 2 of 2	1

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37329 AN: 151902 Hom.: 4813 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.239

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

GnomAD4 genome AF: 0.246 AC: 37351 AN: 152020 Hom.: 4818 Cov.: 32 AF XY: 0.242 AC XY: 17992 AN XY: 74322

African (AFR) AF: 0.198 AC: 8199 AN: 41490

American (AMR) AF: 0.214 AC: 3275 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3470

East Asian (EAS) AF: 0.181 AC: 935 AN: 5160

South Asian (SAS) AF: 0.113 AC: 544 AN: 4818

European-Finnish (FIN) AF: 0.270 AC: 2857 AN: 10586

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.292 AC: 19860 AN: 67918

Other (OTH) AF: 0.236 AC: 498 AN: 2108

Alfa AF: 0.268 Hom.: 9407

Bravo AF: 0.241

Asia WGS AF: 0.146 AC: 507 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.2
DANN	Benign	0.72
PhyloP100		0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11018528; hg19: chr11-88930377; COSMIC: COSV54474524;