rs1074158

Variant names:

• chr2-210310319-A-G
• rs1074158
• NM_079420.3:c.132+4592T>C

Variant summary

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

The NM_079420.3(MYL1):​c.132+4592T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 151,788 control chromosomes in the GnomAD database, including 9,785 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 0.34 (9785 hom., cov: 32)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.459
• Publications: 1 publications found

Genes affected

MYL1 (HGNC:7582): (myosin light chain 1) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

MYL1 Gene-Disease associations (from GenCC):

• congenital myopathy with reduced type 2 muscle fibers

  Inheritance: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, G2P
• congenital myopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000279317 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL1	NM_079420.3	c.132+4592T>C		intron_variant	Intron 1 of 6	ENST00000352451.4	NP_524144.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL1	ENST00000352451.4	c.132+4592T>C		intron_variant	Intron 1 of 6	1	NM_079420.3	ENSP00000307280.4
ENSG00000279317	ENST00000795993.1	n.388+30458A>G		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52213 AN: 151670 Hom.: 9772 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.481

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.441

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.375

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

GnomAD4 genome AF: 0.344 AC: 52249 AN: 151788 Hom.: 9785 Cov.: 32 AF XY: 0.353 AC XY: 26183 AN XY: 74170

African (AFR) AF: 0.185 AC: 7678 AN: 41472

American (AMR) AF: 0.482 AC: 7330 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1510 AN: 3462

East Asian (EAS) AF: 0.440 AC: 2272 AN: 5158

South Asian (SAS) AF: 0.391 AC: 1886 AN: 4820

European-Finnish (FIN) AF: 0.456 AC: 4803 AN: 10530

Middle Eastern (MID) AF: 0.486 AC: 142 AN: 292

European-Non Finnish (NFE) AF: 0.374 AC: 25360 AN: 67814

Other (OTH) AF: 0.376 AC: 793 AN: 2110

Alfa AF: 0.366 Hom.: 37060

Bravo AF: 0.338

Asia WGS AF: 0.436 AC: 1508 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.61
PhyloP100		0.46
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1074158; hg19: chr2-211175043;