rs16844288

Variant names:

• chr2-210302991-C-T
• rs16844288
• NM_079420.3:c.133-476G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-210302991-C-T
• chr2-210302991-C-A

Variant summary

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

The NM_079420.3(MYL1):​c.133-476G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.404 in 586,034 control chromosomes in the GnomAD database, including 48,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.41 (12616 hom., cov: 32)
  • Exomes 𝑓: 0.40 (36112 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.793
• 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: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• congenital myopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ENSG00000279317 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-210302991-C-T is Benign according to our data. Variant chr2-210302991-C-T is described in ClinVar as Benign. ClinVar VariationId is 1294865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_079420.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	NM_079420.3	MANE Select	c.133-476G>A		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.4-199G>A		intron	N/A	NP_524146.1	P05976-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	ENST00000352451.4	TSL:1 MANE Select	c.133-476G>A		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000341685.8	TSL:1	c.4-199G>A		intron	N/A	ENSP00000343321.4	P05976-2
	MYL1	ENST00000957378.1		c.133-476G>A		intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61611 AN: 151844 Hom.: 12574 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.438

Gnomad EAS AF: 0.451

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.460

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.375

Gnomad OTH AF: 0.417

GnomAD4 exome AF: 0.403 AC: 174783 AN: 434072 Hom.: 36112 Cov.: 4 AF XY: 0.404 AC XY: 92032 AN XY: 227714

African (AFR) AF: 0.394 AC: 4674 AN: 11868

American (AMR) AF: 0.534 AC: 8593 AN: 16078

Ashkenazi Jewish (ASJ) AF: 0.431 AC: 5716 AN: 13276

East Asian (EAS) AF: 0.450 AC: 13545 AN: 30124

South Asian (SAS) AF: 0.461 AC: 17986 AN: 39040

European-Finnish (FIN) AF: 0.449 AC: 15818 AN: 35248

Middle Eastern (MID) AF: 0.490 AC: 927 AN: 1892

European-Non Finnish (NFE) AF: 0.372 AC: 97310 AN: 261392

Other (OTH) AF: 0.406 AC: 10214 AN: 25154

GnomAD4 genome AF: 0.406 AC: 61716 AN: 151962 Hom.: 12616 Cov.: 32 AF XY: 0.415 AC XY: 30793 AN XY: 74276

African (AFR) AF: 0.391 AC: 16199 AN: 41448

American (AMR) AF: 0.501 AC: 7644 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.438 AC: 1521 AN: 3472

East Asian (EAS) AF: 0.451 AC: 2325 AN: 5154

South Asian (SAS) AF: 0.460 AC: 2218 AN: 4824

European-Finnish (FIN) AF: 0.460 AC: 4852 AN: 10548

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.375 AC: 25455 AN: 67942

Other (OTH) AF: 0.418 AC: 884 AN: 2114

Alfa AF: 0.244 Hom.: 580

Bravo AF: 0.406

Asia WGS AF: 0.497 AC: 1725 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.13
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs16844288; hg19: chr2-211167715;