Genetic Variant TYR:c.1184+23846C>T (chr11-89251816-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000372.5(TYR):c.1184+23846C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0596 in 151,716 control chromosomes in the GnomAD database, including 339 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 0.060 ( 339 hom., cov: 32)

Consequence

TYR
NM_000372.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.593

Publications

7 publications found

Variant links:

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

TYR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TYR	NM_000372.5 link	c.1184+23846C>T		intron_variant	Intron 3 of 4	ENST00000263321.6	NP_000363.1	P14679-1L8B082
TYR	XM_011542970.3 link	c.1184+23846C>T		intron_variant	Intron 3 of 5		XP_011541272.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TYR	ENST00000263321.6 link	c.1184+23846C>T		intron_variant	Intron 3 of 4	1	NM_000372.5	ENSP00000263321.4		P14679-1

Frequencies

GnomAD3 genomes

AF:

0.0596

AC:

9033

AN:

151598

Hom.:

336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0991

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.0616

Gnomad ASJ

AF:

0.0344

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.0907

Gnomad FIN

AF:

0.0341

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.0310

Gnomad OTH

AF:

0.0666

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

GnomAD4 genome

AF:

0.0596

AC:

9047

AN:

151716

Hom.:

339

Cov.:

AF XY:

0.0612

AC XY:

4535

AN XY:

74128

show subpopulations

African (AFR)

AF:

0.0992

AC:

4111

AN:

41446

American (AMR)

AF:

0.0615

AC:

934

AN:

15180

Ashkenazi Jewish (ASJ)

AF:

0.0344

AC:

119

AN:

3456

East Asian (EAS)

AF:

0.115

AC:

593

AN:

5144

South Asian (SAS)

AF:

0.0902

AC:

434

AN:

4812

European-Finnish (FIN)

AF:

0.0341

AC:

361

AN:

10594

Middle Eastern (MID)

AF:

0.102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0310

AC:

2101

AN:

67768

Other (OTH)

AF:

0.0678

AC:

143

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

430

861

1291

1722

2152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0392

Hom.:

168

Bravo

AF:

0.0615

Asia WGS

AF:

0.0950

AC:

328

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.5

(source)

DANN

Benign

0.71

PhyloP100

0.59

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over