chr1-171651439-A-G

Position:

• chr1-171651439-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000261.2(MYOC):​c.604+569T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 151,766 control chromosomes in the GnomAD database, including 42,404 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 0.75 (42404 hom., cov: 29)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.713

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.86 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOC	NM_000261.2	c.604+569T>C		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+569T>C		intron_variant		1	NM_000261.2	ENSP00000037502.5
MYOC	ENST00000638471.1	n.130+1043T>C		intron_variant		5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.745 AC: 113052 AN: 151648 Hom.: 42360 Cov.: 29

Gnomad AFR AF: 0.803

Gnomad AMI AF: 0.693

Gnomad AMR AF: 0.697

Gnomad ASJ AF: 0.782

Gnomad EAS AF: 0.880

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.730

Gnomad MID AF: 0.816

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.757

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

GnomAD4 genome AF: 0.746 AC: 113152 AN: 151766 Hom.: 42404 Cov.: 29 AF XY: 0.749 AC XY: 55536 AN XY: 74138

Gnomad4 AFR AF: 0.804

Gnomad4 AMR AF: 0.697

Gnomad4 ASJ AF: 0.782

Gnomad4 EAS AF: 0.881

Gnomad4 SAS AF: 0.809

Gnomad4 FIN AF: 0.730

Gnomad4 NFE AF: 0.707

Gnomad4 OTH AF: 0.755

Alfa AF: 0.716 Hom.: 51723

Bravo AF: 0.742

Asia WGS AF: 0.822 AC: 2863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	15
DANN	Benign	0.88

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs235917; hg19: chr1-171620579;