rs2603127

Positions:

• chr3-108524704-G-A
• chr3-108524704-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000273353.5(MYH15):​c.-58+4559C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,926 control chromosomes in the GnomAD database, including 2,177 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 0.15 (2177 hom., cov: 32)
• Consequence: MYH15 ENST00000273353.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LOC124909406 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH15	XM_011512559.3	c.3+4559C>T		intron_variant
LOC124909406	XR_007096000.1			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH15	ENST00000273353.5	c.-58+4559C>T		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23080 AN: 151808 Hom.: 2175 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.152 AC: 23078 AN: 151926 Hom.: 2177 Cov.: 32 AF XY: 0.148 AC XY: 10990 AN XY: 74250

Gnomad4 AFR AF: 0.0495

Gnomad4 AMR AF: 0.147

Gnomad4 ASJ AF: 0.221

Gnomad4 EAS AF: 0.00193

Gnomad4 SAS AF: 0.0782

Gnomad4 FIN AF: 0.168

Gnomad4 NFE AF: 0.223

Gnomad4 OTH AF: 0.180

Alfa AF: 0.208 Hom.: 4525

Bravo AF: 0.148

Asia WGS AF: 0.0440 AC: 157 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.58

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

LitVar

Other links and lift over

dbSNP: rs2603127; hg19: chr3-108243551;