rs1827430

Variant names:

• chr11-89285272-A-G
• rs1827430
• NM_000372.5:c.1366+318A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-89285272-A-G
• chr11-89285272-A-T

Variant summary

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

The NM_000372.5(TYR):​c.1366+318A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,388 control chromosomes in the GnomAD database, including 16,341 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 0.44 (16341 hom., cov: 31)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.77
• Publications: 8 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=-1.05).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYR	NM_000372.5	c.1366+318A>G		intron_variant	Intron 4 of 4	ENST00000263321.6	NP_000363.1
TYR	XM_011542970.3	c.1366+318A>G		intron_variant	Intron 4 of 5		XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6	c.1366+318A>G		intron_variant	Intron 4 of 4	1	NM_000372.5	ENSP00000263321.4
TYR	ENST00000528243.1	n.364+318A>G		intron_variant	Intron 2 of 2	5

Frequencies

GnomAD3 genomes AF: 0.443 AC: 67071 AN: 151270 Hom.: 16302 Cov.: 31

Gnomad AFR AF: 0.662

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.332

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.414

Gnomad MID AF: 0.385

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.444 AC: 67171 AN: 151388 Hom.: 16341 Cov.: 31 AF XY: 0.440 AC XY: 32523 AN XY: 73954

African (AFR) AF: 0.663 AC: 27396 AN: 41340

American (AMR) AF: 0.333 AC: 5042 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1226 AN: 3446

East Asian (EAS) AF: 0.287 AC: 1459 AN: 5086

South Asian (SAS) AF: 0.239 AC: 1149 AN: 4808

European-Finnish (FIN) AF: 0.414 AC: 4355 AN: 10530

Middle Eastern (MID) AF: 0.394 AC: 115 AN: 292

European-Non Finnish (NFE) AF: 0.374 AC: 25303 AN: 67724

Other (OTH) AF: 0.417 AC: 871 AN: 2090

Alfa AF: 0.303 Hom.: 1079

Bravo AF: 0.449

Asia WGS AF: 0.306 AC: 1064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.014
DANN	Benign	0.37
PhyloP100		-3.8
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: rs1827430; hg19: chr11-89018440;