rs16864720

Positions:

• chr1-171643127-G-A

Variant summary

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

The NM_000261.2(MYOC):​c.605-4405C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 152,088 control chromosomes in the GnomAD database, including 1,865 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 0.15 (1865 hom., cov: 31)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455

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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOC	NM_000261.2	c.605-4405C>T		intron_variant		ENST00000037502.11	NP_000252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOC	ENST00000037502.11	c.605-4405C>T		intron_variant		1	NM_000261.2	ENSP00000037502	P1
MYOC	ENST00000638471.1	c.134+261C>T		intron_variant, NMD_transcript_variant		5		ENSP00000491206

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22855 AN: 151970 Hom.: 1867 Cov.: 31

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.0172

Gnomad SAS AF: 0.202

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.150 AC: 22873 AN: 152088 Hom.: 1865 Cov.: 31 AF XY: 0.150 AC XY: 11173 AN XY: 74358

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.182

Alfa AF: 0.166 Hom.: 2970

Bravo AF: 0.148

Asia WGS AF: 0.0920 AC: 321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.80

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: rs16864720; hg19: chr1-171612267;