rs12804012

Variant names:

• chr11-89227622-G-A
• rs12804012
• NM_000372.5:c.1037-201G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-89227622-G-A
• chr11-89227622-G-C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000372.5(TYR):​c.1037-201G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.229 in 151,918 control chromosomes in the GnomAD database, including 6,298 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (6298 hom., cov: 32)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.467
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 11-89227622-G-A is Benign according to our data. Variant chr11-89227622-G-A is described in ClinVar as Benign. ClinVar VariationId is 1238697.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.498 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYR	NM_000372.5	MANE Select	c.1037-201G>A		intron	N/A	NP_000363.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TYR	ENST00000263321.6	TSL:1 MANE Select	c.1037-201G>A		intron	N/A	ENSP00000263321.4

Frequencies

GnomAD3 genomes AF: 0.229 AC: 34744 AN: 151800 Hom.: 6263 Cov.: 32

Gnomad AFR AF: 0.503

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.166

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.124

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.139

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.108

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.229 AC: 34838 AN: 151918 Hom.: 6298 Cov.: 32 AF XY: 0.228 AC XY: 16924 AN XY: 74222

African (AFR) AF: 0.504 AC: 20865 AN: 41416

American (AMR) AF: 0.166 AC: 2530 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 409 AN: 3466

East Asian (EAS) AF: 0.124 AC: 642 AN: 5166

South Asian (SAS) AF: 0.203 AC: 980 AN: 4818

European-Finnish (FIN) AF: 0.139 AC: 1473 AN: 10560

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

European-Non Finnish (NFE) AF: 0.108 AC: 7339 AN: 67930

Other (OTH) AF: 0.229 AC: 484 AN: 2110

Alfa AF: 0.168 Hom.: 1114

Bravo AF: 0.242

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.23
PhyloP100		0.47
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: rs12804012; hg19: chr11-88960790;