chr1-171648188-TAA-T

Position:

• chr1-171648188-TAA-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_000261.2(MYOC):​c.604+3818_604+3819delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0089 (14 hom., cov: 0)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.329

Genes affected

MYOC (HGNC:7610): (myocilin) MYOC encodes the protein myocilin, which is believed to have a role in cytoskeletal function. MYOC is expressed in many occular tissues, including the trabecular meshwork, and was revealed to be the trabecular meshwork glucocorticoid-inducible response protein (TIGR). The trabecular meshwork is a specialized eye tissue essential in regulating intraocular pressure, and mutations in MYOC have been identified as the cause of hereditary juvenile-onset open-angle glaucoma. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00889 (1285/144602) while in subpopulation AFR AF= 0.0219 (861/39296). AF 95% confidence interval is 0.0207. There are 14 homozygotes in gnomad4. There are 635 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 14 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOC	NM_000261.2	c.604+3818_604+3819delTT		intron_variant		ENST00000037502.11	NP_000252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOC	ENST00000037502.11	c.604+3818_604+3819delTT		intron_variant		1	NM_000261.2	ENSP00000037502.5
MYOC	ENST00000638471.1	n.130+4292_130+4293delTT		intron_variant		5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.00883 AC: 1277 AN: 144568 Hom.: 14 Cov.: 0

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00552

Gnomad ASJ AF: 0.0123

Gnomad EAS AF: 0.00304

Gnomad SAS AF: 0.000665

Gnomad FIN AF: 0.0130

Gnomad MID AF: 0.00662

Gnomad NFE AF: 0.00226

Gnomad OTH AF: 0.00918

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

GnomAD4 genome AF: 0.00889 AC: 1285 AN: 144602 Hom.: 14 Cov.: 0 AF XY: 0.00910 AC XY: 635 AN XY: 69814

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.00545

Gnomad4 ASJ AF: 0.0123

Gnomad4 EAS AF: 0.00305

Gnomad4 SAS AF: 0.000892

Gnomad4 FIN AF: 0.0130

Gnomad4 NFE AF: 0.00226

Gnomad4 OTH AF: 0.00909

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs11295938; hg19: chr1-171617328;