rs12804012

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TYR	NM_000372.5	c.1037-201G>A		intron_variant		ENST00000263321.6
TYR	XM_011542970.3	c.1037-201G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TYR	ENST00000263321.6	c.1037-201G>A		intron_variant		1	NM_000372.5	P1

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

Gnomad4 AFR AF: 0.504

Gnomad4 AMR AF: 0.166

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.124

Gnomad4 SAS AF: 0.203

Gnomad4 FIN AF: 0.139

Gnomad4 NFE AF: 0.108

Gnomad4 OTH AF: 0.229

Alfa AF: 0.161 Hom.: 530

Bravo AF: 0.242

Asia WGS AF: 0.203 AC: 705 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.2
DANN	Benign	0.23

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

Publications

LitVar

Other links and lift over

dbSNP: rs12804012; hg19: chr11-88960790;