rs1393350

Variant names:

• chr11-89277878-G-A
• rs1393350
• NM_000372.5:c.1185-6895G>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.1185-6895G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,478 control chromosomes in the GnomAD database, including 2,973 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 0.17 (2973 hom., cov: 31)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0750
• Publications: 157 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYR	NM_000372.5	c.1185-6895G>A		intron_variant	Intron 3 of 4	ENST00000263321.6	NP_000363.1
TYR	XM_011542970.3	c.1185-6895G>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.1185-6895G>A		intron_variant	Intron 3 of 4	1	NM_000372.5	ENSP00000263321.4

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25614 AN: 151360 Hom.: 2971 Cov.: 31

Gnomad AFR AF: 0.0468

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.00215

Gnomad SAS AF: 0.0620

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.266

Gnomad OTH AF: 0.182

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

GnomAD4 genome AF: 0.169 AC: 25612 AN: 151478 Hom.: 2973 Cov.: 31 AF XY: 0.161 AC XY: 11907 AN XY: 73992

African (AFR) AF: 0.0467 AC: 1934 AN: 41410

American (AMR) AF: 0.153 AC: 2318 AN: 15168

Ashkenazi Jewish (ASJ) AF: 0.232 AC: 801 AN: 3458

East Asian (EAS) AF: 0.00215 AC: 11 AN: 5108

South Asian (SAS) AF: 0.0629 AC: 303 AN: 4816

European-Finnish (FIN) AF: 0.156 AC: 1644 AN: 10528

Middle Eastern (MID) AF: 0.195 AC: 57 AN: 292

European-Non Finnish (NFE) AF: 0.266 AC: 17986 AN: 67676

Other (OTH) AF: 0.180 AC: 380 AN: 2110

Alfa AF: 0.232 Hom.: 20934

Bravo AF: 0.164

Asia WGS AF: 0.0320 AC: 113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.9
DANN	Benign	0.84
PhyloP100		-0.075
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: rs1393350; hg19: chr11-89011046;