1-171638562-C-T

Variant names:

• chr1-171638562-C-T
• rs2032555
• NM_000261.2:c.730+35G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000261.2(MYOC):​c.730+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.722 in 1,611,202 control chromosomes in the GnomAD database, including 422,233 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44199 hom., cov: 31)
  • Exomes 𝑓: 0.72 (378034 hom.)
• Consequence: MYOC NM_000261.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -5.89
• Publications: 24 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 1-171638562-C-T is Benign according to our data. Variant chr1-171638562-C-T is described in ClinVar as Benign. ClinVar VariationId is 1259809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.859 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOC	NM_000261.2	c.730+35G>A		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.730+35G>A		intron_variant	Intron 2 of 2	1	NM_000261.2	ENSP00000037502.5
MYOCOS	ENST00000637303.1	c.235-68C>T		intron_variant	Intron 3 of 3	5		ENSP00000490048.1
MYOC	ENST00000638471.1	n.*68+35G>A		intron_variant	Intron 3 of 3	5		ENSP00000491206.1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115307 AN: 152002 Hom.: 44146 Cov.: 31

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.692

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.790

Gnomad EAS AF: 0.773

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.707

Gnomad OTH AF: 0.763

GnomAD2 exomes AF: 0.722 AC: 181475 AN: 251352 AF XY: 0.728

Gnomad AFR exome AF: 0.861

Gnomad AMR exome AF: 0.597

Gnomad ASJ exome AF: 0.795

Gnomad EAS exome AF: 0.771

Gnomad FIN exome AF: 0.702

Gnomad NFE exome AF: 0.705

Gnomad OTH exome AF: 0.727

GnomAD4 exome AF: 0.718 AC: 1047906 AN: 1459082 Hom.: 378034 Cov.: 35 AF XY: 0.722 AC XY: 523823 AN XY: 725936

African (AFR) AF: 0.867 AC: 28998 AN: 33434

American (AMR) AF: 0.608 AC: 27158 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.789 AC: 20586 AN: 26092

East Asian (EAS) AF: 0.795 AC: 31518 AN: 39626

South Asian (SAS) AF: 0.813 AC: 70017 AN: 86174

European-Finnish (FIN) AF: 0.704 AC: 37531 AN: 53308

Middle Eastern (MID) AF: 0.809 AC: 4664 AN: 5764

European-Non Finnish (NFE) AF: 0.706 AC: 783062 AN: 1109724

Other (OTH) AF: 0.736 AC: 44372 AN: 60260

GnomAD4 genome AF: 0.759 AC: 115416 AN: 152120 Hom.: 44199 Cov.: 31 AF XY: 0.760 AC XY: 56535 AN XY: 74346

African (AFR) AF: 0.866 AC: 35969 AN: 41520

American (AMR) AF: 0.699 AC: 10682 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.790 AC: 2742 AN: 3472

East Asian (EAS) AF: 0.773 AC: 3983 AN: 5152

South Asian (SAS) AF: 0.806 AC: 3884 AN: 4820

European-Finnish (FIN) AF: 0.718 AC: 7585 AN: 10564

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.707 AC: 48089 AN: 68004

Other (OTH) AF: 0.761 AC: 1602 AN: 2106

Alfa AF: 0.724 Hom.: 63021

Bravo AF: 0.755

Asia WGS AF: 0.785 AC: 2732 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 28792703, 16863615) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.015
DANN	Benign	0.55
PhyloP100		-5.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2032555; hg19: chr1-171607702; COSMIC: COSV50675059;