rs6425363

Positions:

• chr1-171648253-C-T

Variant summary

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

The NM_000261.2(MYOC):​c.604+3755G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0939 in 151,890 control chromosomes in the GnomAD database, including 685 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 0.094 (685 hom., cov: 31)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOC	NM_000261.2	c.604+3755G>A		intron_variant		ENST00000037502.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOC	ENST00000037502.11	c.604+3755G>A		intron_variant		1	NM_000261.2	P1
MYOC	ENST00000638471.1	c.130+4229G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0939 AC: 14248 AN: 151778 Hom.: 681 Cov.: 31

Gnomad AFR AF: 0.0765

Gnomad AMI AF: 0.0833

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.0879

Gnomad FIN AF: 0.113

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0912

Gnomad OTH AF: 0.0874

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

GnomAD4 genome AF: 0.0939 AC: 14261 AN: 151890 Hom.: 685 Cov.: 31 AF XY: 0.0960 AC XY: 7127 AN XY: 74228

Gnomad4 AFR AF: 0.0764

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.101

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.113

Gnomad4 NFE AF: 0.0912

Gnomad4 OTH AF: 0.0932

Alfa AF: 0.0892 Hom.: 87

Bravo AF: 0.0935

Asia WGS AF: 0.197 AC: 685 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.76
DANN	Benign	0.55

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: rs6425363; hg19: chr1-171617393; COSMIC: COSV50674388;