chr1-171648188-T-TA

Variant names:

• chr1-171648188-T-TA
• rs11295938
• NM_000261.2:c.604+3819dupT

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_000261.2(MYOC):​c.604+3819dupT 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 0.00035 (0 hom., cov: 0)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.297
• 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: Likely_benign. The variant received -1 ACMG points.

• BS2: High AC in GnomAd4 at 51 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOC	NM_000261.2	c.604+3819dupT		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+3819_604+3820insT		intron_variant	Intron 1 of 2	1	NM_000261.2	ENSP00000037502.5
MYOC	ENST00000638471.1	n.130+4293_130+4294insT		intron_variant	Intron 1 of 3	5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.000352 AC: 51 AN: 144778 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000662

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000345

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00141

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000452

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000121

Gnomad OTH AF: 0.000510

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

GnomAD4 genome AF: 0.000352 AC: 51 AN: 144812 Hom.: 0 Cov.: 0 AF XY: 0.000272 AC XY: 19 AN XY: 69928

African (AFR) AF: 0.000661 AC: 26 AN: 39334

American (AMR) AF: 0.000344 AC: 5 AN: 14518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3414

East Asian (EAS) AF: 0.00142 AC: 7 AN: 4932

South Asian (SAS) AF: 0.00 AC: 0 AN: 4490

European-Finnish (FIN) AF: 0.000452 AC: 4 AN: 8840

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 280

European-Non Finnish (NFE) AF: 0.000121 AC: 8 AN: 66126

Other (OTH) AF: 0.000505 AC: 1 AN: 1982

Alfa AF: 0.000391 Hom.: 1013

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.30

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;