Genetic Variant MYOC:c.731-73C>T (chr1-171636782-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_000261.2(MYOC):c.731-73C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0258 in 1,537,068 control chromosomes in the GnomAD database, including 682 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. The gene MYOC is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.021 ( 56 hom., cov: 32)

Exomes 𝑓: 0.026 ( 626 hom. )

Consequence

MYOC
NM_000261.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.401

Publications

2 publications found

Variant links:

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]

MYOC links:

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

MYOCOS links:

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ACMG classification

Specifications for MYOC are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0206 (3142/152262) while in subpopulation NFE AF = 0.0299 (2037/68022). AF 95% confidence interval is 0.0289. There are 56 homozygotes in GnomAd4. There are 1481 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 3142 AD gene.

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.731-73C>T		intron	N/A	NP_000252.1	Q99972

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYOC	ENST00000037502.11	TSL:1 MANE Select	c.731-73C>T		intron	N/A	ENSP00000037502.5	Q99972
MYOC	ENST00000971579.1		c.763C>T	p.Arg255Cys	missense	Exon 3 of 3	ENSP00000641638.1
MYOC	ENST00000877923.1		c.797-73C>T		intron	N/A	ENSP00000547982.1

Frequencies

GnomAD3 genomes

AF:

0.0207

AC:

3142

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00478

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0261

Gnomad ASJ

AF:

0.0703

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0164

Gnomad FIN

AF:

0.00923

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0300

Gnomad OTH

AF:

0.0306

GnomAD4 exome

AF:

0.0264

AC:

36521

AN:

1384806

Hom.:

626

AF XY:

0.0265

AC XY:

18358

AN XY:

692444

show subpopulations

African (AFR)

AF:

0.00472

AC:

152

AN:

32174

American (AMR)

AF:

0.0198

AC:

870

AN:

44050

Ashkenazi Jewish (ASJ)

AF:

0.0815

AC:

2093

AN:

25670

East Asian (EAS)

AF:

0.0000508

AC:

AN:

39372

South Asian (SAS)

AF:

0.0165

AC:

1386

AN:

83942

European-Finnish (FIN)

AF:

0.0102

AC:

398

AN:

38902

Middle Eastern (MID)

AF:

0.0550

AC:

311

AN:

5656

European-Non Finnish (NFE)

AF:

0.0279

AC:

29535

AN:

1056842

Other (OTH)

AF:

0.0305

AC:

1774

AN:

58198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1819

3639

5458

7278

9097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1062

2124

3186

4248

5310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0206

AC:

3142

AN:

152262

Hom.:

Cov.:

AF XY:

0.0199

AC XY:

1481

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.00481

AC:

200

AN:

41542

American (AMR)

AF:

0.0261

AC:

399

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0703

AC:

244

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5180

South Asian (SAS)

AF:

0.0164

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00923

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.0646

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0299

AC:

2037

AN:

68022

Other (OTH)

AF:

0.0308

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

157

314

472

629

786

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

126

168

210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0313

Hom.:

Bravo

AF:

0.0207

Asia WGS

AF:

0.00693

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.4

(source)

DANN

Benign

0.57

PhyloP100

-0.40

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over