rs3793975

Variant names:

• chr11-89228020-G-A
• rs3793975
• NM_000372.5:c.1184+50G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000372.5(TYR):​c.1184+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,596,530 control chromosomes in the GnomAD database, including 14,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2607 hom., cov: 32)
  • Exomes 𝑓: 0.12 (12048 hom.)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.107
• Publications: 11 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: Orphanet, G2P, 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-89228020-G-A is Benign according to our data. Variant chr11-89228020-G-A is described in ClinVar as Benign. ClinVar VariationId is 1281825.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.284 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000372.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYR	NM_000372.5	MANE Select	c.1184+50G>A		intron	N/A	NP_000363.1	P14679-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYR	ENST00000263321.6	TSL:1 MANE Select	c.1184+50G>A		intron	N/A	ENSP00000263321.4	P14679-1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25355 AN: 151862 Hom.: 2587 Cov.: 32

Gnomad AFR AF: 0.288

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.123

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.140 AC: 34747 AN: 248150 AF XY: 0.140

Gnomad AFR exome AF: 0.292

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.111

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.128

GnomAD4 exome AF: 0.122 AC: 176056 AN: 1444552 Hom.: 12048 Cov.: 27 AF XY: 0.124 AC XY: 89574 AN XY: 719698

African (AFR) AF: 0.297 AC: 9844 AN: 33114

American (AMR) AF: 0.135 AC: 6018 AN: 44582

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 3074 AN: 25992

East Asian (EAS) AF: 0.149 AC: 5897 AN: 39538

South Asian (SAS) AF: 0.210 AC: 18012 AN: 85966

European-Finnish (FIN) AF: 0.135 AC: 6821 AN: 50588

Middle Eastern (MID) AF: 0.197 AC: 1128 AN: 5738

European-Non Finnish (NFE) AF: 0.107 AC: 117281 AN: 1099134

Other (OTH) AF: 0.133 AC: 7981 AN: 59900

GnomAD4 genome AF: 0.167 AC: 25421 AN: 151978 Hom.: 2607 Cov.: 32 AF XY: 0.168 AC XY: 12483 AN XY: 74234

African (AFR) AF: 0.288 AC: 11959 AN: 41472

American (AMR) AF: 0.142 AC: 2171 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 410 AN: 3472

East Asian (EAS) AF: 0.123 AC: 631 AN: 5134

South Asian (SAS) AF: 0.202 AC: 973 AN: 4808

European-Finnish (FIN) AF: 0.139 AC: 1466 AN: 10556

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.108 AC: 7309 AN: 67966

Other (OTH) AF: 0.182 AC: 386 AN: 2116

Alfa AF: 0.134 Hom.: 1113

Bravo AF: 0.172

Asia WGS AF: 0.191 AC: 663 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.23
DANN	Benign	0.52
PhyloP100		-0.11
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: rs3793975; hg19: chr11-88961188; COSMIC: COSV54477229;