rs2075648

chr1-171652694-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The 1-171652694-C-T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,592,502 control chromosomes in the GnomAD database, including 18,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.11 (1258 hom., cov: 32)
  • Exomes 𝑓: 0.14 (16976 hom.)
• Consequence: MYOC NM_000261.2 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.12

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 1-171652694-C-T is Benign according to our data. Variant chr1-171652694-C-T is described in ClinVar as [Benign]. Clinvar id is 1260300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYOC	NM_000261.2			upstream_gene_variant		ENST00000037502.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOC	ENST00000037502.11			upstream_gene_variant		1	NM_000261.2	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16690 AN: 152016 Hom.: 1257 Cov.: 32

Gnomad AFR AF: 0.0324

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0759

Gnomad SAS AF: 0.346

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.114

GnomAD4 exome AF: 0.142 AC: 203981 AN: 1440368 Hom.: 16976 Cov.: 30 AF XY: 0.148 AC XY: 106237 AN XY: 715776

Gnomad4 AFR exome AF: 0.0313

Gnomad4 AMR exome AF: 0.102

Gnomad4 ASJ exome AF: 0.133

Gnomad4 EAS exome AF: 0.0568

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.164

Gnomad4 NFE exome AF: 0.134

Gnomad4 OTH exome AF: 0.138

GnomAD4 genome AF: 0.110 AC: 16700 AN: 152134 Hom.: 1258 Cov.: 32 AF XY: 0.114 AC XY: 8459 AN XY: 74360

Gnomad4 AFR AF: 0.0323

Gnomad4 AMR AF: 0.102

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0763

Gnomad4 SAS AF: 0.347

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.133

Gnomad4 OTH AF: 0.113

Alfa AF: 0.127 Hom.: 1265

Bravo AF: 0.0958

Asia WGS AF: 0.200 AC: 696 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.15
Dann	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2075648; hg19: chr1-171621834; COSMIC: COSV50674517;