chr1-171637599-T-C

Position:

• chr1-171637599-T-C

Variant summary

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

The NM_000261.2(MYOC):​c.731-890A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 151,680 control chromosomes in the GnomAD database, including 1,252 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 0.12 (1252 hom., cov: 31)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.164

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]

MYOCOS (HGNC:53429): (myocilin opposite strand)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.176 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOC	NM_000261.2	c.731-890A>G		intron_variant		ENST00000037502.11	NP_000252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYOC	ENST00000037502.11	c.731-890A>G		intron_variant		1	NM_000261.2	ENSP00000037502.5
MYOCOS	ENST00000637303.1	c.235-1031T>C		intron_variant		5		ENSP00000490048.1
MYOC	ENST00000638471.1	n.*69-890A>G		intron_variant		5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18847 AN: 151572 Hom.: 1254 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0168

Gnomad SAS AF: 0.185

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.124 AC: 18863 AN: 151680 Hom.: 1252 Cov.: 31 AF XY: 0.126 AC XY: 9312 AN XY: 74114

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.120

Gnomad4 ASJ AF: 0.212

Gnomad4 EAS AF: 0.0174

Gnomad4 SAS AF: 0.186

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.151

Alfa AF: 0.125 Hom.: 1560

Bravo AF: 0.121

Asia WGS AF: 0.0840 AC: 290 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.51

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: rs7545646; hg19: chr1-171606739;