chr11-89270436-C-A

Variant names:

• chr11-89270436-C-A
• rs2298458
• NM_000372.5:c.1185-14337C>A

Variant summary

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

The NM_000372.5(TYR):​c.1185-14337C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0648 in 151,878 control chromosomes in the GnomAD database, including 444 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 0.065 (444 hom., cov: 32)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0560
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.118 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYR	NM_000372.5	c.1185-14337C>A		intron_variant	Intron 3 of 4	ENST00000263321.6	NP_000363.1
TYR	XM_011542970.3	c.1185-14337C>A		intron_variant	Intron 3 of 5		XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6	c.1185-14337C>A		intron_variant	Intron 3 of 4	1	NM_000372.5	ENSP00000263321.4

Frequencies

GnomAD3 genomes AF: 0.0647 AC: 9824 AN: 151760 Hom.: 440 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.242

Gnomad AMR AF: 0.0645

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0922

Gnomad FIN AF: 0.0338

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0310

Gnomad OTH AF: 0.0734

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

GnomAD4 genome AF: 0.0648 AC: 9846 AN: 151878 Hom.: 444 Cov.: 32 AF XY: 0.0664 AC XY: 4925 AN XY: 74216

African (AFR) AF: 0.116 AC: 4790 AN: 41458

American (AMR) AF: 0.0644 AC: 981 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3466

East Asian (EAS) AF: 0.126 AC: 644 AN: 5108

South Asian (SAS) AF: 0.0917 AC: 442 AN: 4822

European-Finnish (FIN) AF: 0.0338 AC: 359 AN: 10608

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0310 AC: 2106 AN: 67880

Other (OTH) AF: 0.0745 AC: 157 AN: 2106

Alfa AF: 0.0388 Hom.: 100

Bravo AF: 0.0677

Asia WGS AF: 0.100 AC: 345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.77
PhyloP100		-0.056
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2298458; hg19: chr11-89003604;