2-210303914-A-G

Variant names:

• chr2-210303914-A-G
• rs1472955
• NM_079420.3:c.133-1399T>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.133-1399T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 151,856 control chromosomes in the GnomAD database, including 12,290 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 0.40 (12290 hom., cov: 31)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.268
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL1	NM_079420.3	c.133-1399T>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.133-1399T>C		intron_variant	Intron 1 of 6	1	NM_079420.3	ENSP00000307280.4
ENSG00000279317	ENST00000795993.1	n.388+24053A>G		intron_variant	Intron 4 of 5

Frequencies

GnomAD3 genomes AF: 0.400 AC: 60769 AN: 151738 Hom.: 12252 Cov.: 31

Gnomad AFR AF: 0.372

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.450

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.414

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

GnomAD4 genome AF: 0.401 AC: 60869 AN: 151856 Hom.: 12290 Cov.: 31 AF XY: 0.409 AC XY: 30396 AN XY: 74230

African (AFR) AF: 0.372 AC: 15426 AN: 41418

American (AMR) AF: 0.499 AC: 7609 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.439 AC: 1518 AN: 3458

East Asian (EAS) AF: 0.450 AC: 2312 AN: 5136

South Asian (SAS) AF: 0.460 AC: 2208 AN: 4804

European-Finnish (FIN) AF: 0.460 AC: 4841 AN: 10532

Middle Eastern (MID) AF: 0.493 AC: 144 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25462 AN: 67942

Other (OTH) AF: 0.415 AC: 874 AN: 2108

Alfa AF: 0.399 Hom.: 1940

Bravo AF: 0.400

Asia WGS AF: 0.496 AC: 1722 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	3.5
DANN	Benign	0.40
PhyloP100		0.27
PromoterAI		0.0069	Neutral
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: rs1472955; hg19: chr2-211168638;