1-171648188-TAAAAA-TAAA

Variant names:

• chr1-171648188-TAA-T
• rs11295938
• NM_000261.2:c.604+3818_604+3819delTT

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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]

MYOC Gene-Disease associations (from GenCC):

• glaucoma 1, open angle, A

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• juvenile open angle glaucoma

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
• open-angle glaucoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• congenital glaucoma

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1285 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOC	NM_000261.2	c.604+3818_604+3819delTT		intron_variant	Intron 1 of 2	ENST00000037502.11	NP_000252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOC	ENST00000037502.11	c.604+3818_604+3819delTT		intron_variant	Intron 1 of 2	1	NM_000261.2	ENSP00000037502.5
MYOC	ENST00000638471.1	n.130+4292_130+4293delTT		intron_variant	Intron 1 of 3	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

African (AFR) AF: 0.0219 AC: 861 AN: 39296

American (AMR) AF: 0.00545 AC: 79 AN: 14508

Ashkenazi Jewish (ASJ) AF: 0.0123 AC: 42 AN: 3414

East Asian (EAS) AF: 0.00305 AC: 15 AN: 4926

South Asian (SAS) AF: 0.000892 AC: 4 AN: 4486

European-Finnish (FIN) AF: 0.0130 AC: 114 AN: 8764

Middle Eastern (MID) AF: 0.0108 AC: 3 AN: 278

European-Non Finnish (NFE) AF: 0.00226 AC: 149 AN: 66054

Other (OTH) AF: 0.00909 AC: 18 AN: 1980

Alfa AF: 0.00 Hom.: 1013

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism

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: rs11295938; hg19: chr1-171617328;