chr1-171645165-T-C

Variant names:

• chr1-171645165-T-C
• rs235877
• NM_000261.2:c.605-6443A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000261.2(MYOC):​c.605-6443A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.756 in 152,106 control chromosomes in the GnomAD database, including 43,839 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 0.76 (43839 hom., cov: 31)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.378
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000261.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOC	NM_000261.2	MANE Select	c.605-6443A>G		intron	N/A	NP_000252.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOC	ENST00000037502.11	TSL:1 MANE Select	c.605-6443A>G		intron	N/A	ENSP00000037502.5
	MYOC	ENST00000638471.1	TSL:5	n.131-1774A>G		intron	N/A	ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114856 AN: 151988 Hom.: 43780 Cov.: 31

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.766

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.708

Gnomad OTH AF: 0.758

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

GnomAD4 genome AF: 0.756 AC: 114970 AN: 152106 Hom.: 43839 Cov.: 31 AF XY: 0.757 AC XY: 56272 AN XY: 74348

African (AFR) AF: 0.857 AC: 35592 AN: 41536

American (AMR) AF: 0.696 AC: 10637 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2742 AN: 3472

East Asian (EAS) AF: 0.767 AC: 3959 AN: 5162

South Asian (SAS) AF: 0.805 AC: 3885 AN: 4828

European-Finnish (FIN) AF: 0.718 AC: 7577 AN: 10558

Middle Eastern (MID) AF: 0.850 AC: 250 AN: 294

European-Non Finnish (NFE) AF: 0.708 AC: 48116 AN: 67976

Other (OTH) AF: 0.755 AC: 1581 AN: 2094

Alfa AF: 0.741 Hom.: 5329

Bravo AF: 0.752

Asia WGS AF: 0.783 AC: 2726 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.41
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs235877; hg19: chr1-171614305;