rs12076134

Variant names:

• chr1-171636914-T-G
• rs12076134
• NM_000261.2:c.731-205A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000261.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOC	NM_000261.2	MANE Select	c.731-205A>C		intron	N/A	NP_000252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOC	ENST00000037502.11	TSL:1 MANE Select	c.731-205A>C		intron	N/A	ENSP00000037502.5
	MYOC	ENST00000971579.1		c.731-100A>C		intron	N/A	ENSP00000641638.1
	MYOC	ENST00000877923.1		c.797-205A>C		intron	N/A	ENSP00000547982.1

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

African (AFR) AF: 0.167 AC: 6953 AN: 41530

American (AMR) AF: 0.224 AC: 3426 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.130 AC: 452 AN: 3468

East Asian (EAS) AF: 0.213 AC: 1102 AN: 5168

South Asian (SAS) AF: 0.373 AC: 1797 AN: 4816

European-Finnish (FIN) AF: 0.248 AC: 2625 AN: 10582

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15017 AN: 67998

Other (OTH) AF: 0.206 AC: 435 AN: 2114

Alfa AF: 0.211 Hom.: 4471

Bravo AF: 0.199

Asia WGS AF: 0.277 AC: 966 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.3
DANN	Benign	0.57
PhyloP100		-0.0080
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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