chr1-171630813-G-A

Variant names:

• chr1-171630813-G-A
• rs2421853
• ENST00000637303.1:c.234+4221G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000637303.1(MYOCOS):​c.234+4221G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 151,916 control chromosomes in the GnomAD database, including 9,330 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 0.33 (9330 hom., cov: 32)
• Consequence: MYOCOS ENST00000637303.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.30
• Publications: 6 publications found

Genes affected

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.506 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOCOS	ENST00000637303.1	c.234+4221G>A		intron_variant	Intron 3 of 3	5		ENSP00000490048.1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50220 AN: 151798 Hom.: 9322 Cov.: 32

Gnomad AFR AF: 0.512

Gnomad AMI AF: 0.140

Gnomad AMR AF: 0.287

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.214

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.331 AC: 50287 AN: 151916 Hom.: 9330 Cov.: 32 AF XY: 0.331 AC XY: 24582 AN XY: 74238

African (AFR) AF: 0.512 AC: 21199 AN: 41388

American (AMR) AF: 0.287 AC: 4372 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 699 AN: 3466

East Asian (EAS) AF: 0.214 AC: 1106 AN: 5160

South Asian (SAS) AF: 0.407 AC: 1958 AN: 4816

European-Finnish (FIN) AF: 0.257 AC: 2714 AN: 10542

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.256 AC: 17394 AN: 67972

Other (OTH) AF: 0.301 AC: 636 AN: 2112

Alfa AF: 0.268 Hom.: 9866

Bravo AF: 0.334

Asia WGS AF: 0.311 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	4.1
DANN	Benign	0.74
PhyloP100		1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2421853; hg19: chr1-171599953;