NM_000261.2:c.731-73C>T

Variant names:

• chr1-171636782-G-A
• rs79255460
• NM_000261.2:c.731-73C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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.

• Frequency:
  • Genomes: 𝑓 0.021 (56 hom., cov: 32)
  • Exomes 𝑓: 0.026 (626 hom.)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401
• Publications: 2 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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOC	NM_000261.2	c.731-73C>T		intron_variant	Intron 2 of 2	ENST00000037502.11	NP_000252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOC	ENST00000037502.11	c.731-73C>T		intron_variant	Intron 2 of 2	1	NM_000261.2	ENSP00000037502.5
MYOCOS	ENST00000637303.1	c.235-1848G>A		intron_variant	Intron 3 of 3	5		ENSP00000490048.1
MYOC	ENST00000638471.1	n.*69-73C>T		intron_variant	Intron 3 of 3	5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.0207 AC: 3142 AN: 152144 Hom.: 56 Cov.: 32

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

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: 2 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

GnomAD4 genome AF: 0.0206 AC: 3142 AN: 152262 Hom.: 56 Cov.: 32 AF XY: 0.0199 AC XY: 1481 AN XY: 74454

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: 1 AN: 5180

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4824

European-Finnish (FIN) AF: 0.00923 AC: 98 AN: 10614

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0299 AC: 2037 AN: 68022

Other (OTH) AF: 0.0308 AC: 65 AN: 2112

Alfa AF: 0.0313 Hom.: 19

Bravo AF: 0.0207

Asia WGS AF: 0.00693 AC: 25 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.4
DANN	Benign	0.57
PhyloP100		-0.40
Mutation Taster		=100/0	polymorphism

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: rs79255460; hg19: chr1-171605922;