rs12076134

Positions:

• chr1-171636914-T-G

Variant summary

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

The NM_000261.2(MYOC):​c.731-205A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.21 in 152,158 control chromosomes in the GnomAD database, including 3,505 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3505 hom., cov: 32)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00800

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 1-171636914-T-G is Benign according to our data. Variant chr1-171636914-T-G is described in ClinVar as [Benign]. Clinvar id is 1285889.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYOC	NM_000261.2	c.731-205A>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.731-205A>C		intron_variant		1	NM_000261.2	ENSP00000037502	P1
MYOCOS	ENST00000637303.1	c.235-1716T>G		intron_variant		5		ENSP00000490048	A2
MYOC	ENST00000638471.1	c.*69-205A>C		intron_variant, NMD_transcript_variant		5		ENSP00000491206

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31972 AN: 152040 Hom.: 3509 Cov.: 32

Gnomad AFR AF: 0.168

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.130

Gnomad EAS AF: 0.213

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.210 AC: 31984 AN: 152158 Hom.: 3505 Cov.: 32 AF XY: 0.213 AC XY: 15875 AN XY: 74386

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.224

Gnomad4 ASJ AF: 0.130

Gnomad4 EAS AF: 0.213

Gnomad4 SAS AF: 0.373

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.206

Alfa AF: 0.213 Hom.: 3494

Bravo AF: 0.199

Asia WGS AF: 0.277 AC: 966 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

Oct 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.57

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: rs12076134; hg19: chr1-171606054; COSMIC: COSV50674643;