rs621313

Positions:

• chr11-89180495-A-G
• chr11-89180495-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000372.5(TYR):​c.819+1723A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,780 control chromosomes in the GnomAD database, including 28,325 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 0.59 (28325 hom., cov: 30)
• Consequence: TYR NM_000372.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.220

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TYR	NM_000372.5	c.819+1723A>G		intron_variant		ENST00000263321.6	NP_000363.1
TYR	XM_011542970.3	c.819+1723A>G		intron_variant			XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6	c.819+1723A>G		intron_variant		1	NM_000372.5	ENSP00000263321	P1
TYR	ENST00000526139.1	n.880+1723A>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.586 AC: 88915 AN: 151660 Hom.: 28266 Cov.: 30

Gnomad AFR AF: 0.855

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.541

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

GnomAD4 genome AF: 0.587 AC: 89045 AN: 151780 Hom.: 28325 Cov.: 30 AF XY: 0.584 AC XY: 43359 AN XY: 74182

Gnomad4 AFR AF: 0.856

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.398

Gnomad4 SAS AF: 0.469

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.542

Alfa AF: 0.507 Hom.: 13490

Bravo AF: 0.592

Asia WGS AF: 0.487 AC: 1693 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.34
DANN	Benign	0.48

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: rs621313; hg19: chr11-88913663;