2-210303478-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_079420.3(MYL1):c.133-963T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0925 in 1,501,884 control chromosomes in the GnomAD database, including 7,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.078 (517 hom., cov: 32)
  • Exomes 𝑓: 0.094 (6756 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.775

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-210303478-A-G is Benign according to our data. Variant chr2-210303478-A-G is described in ClinVar as [Benign]. Clinvar id is 1297941.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3	c.133-963T>C		intron_variant		ENST00000352451.4
MYL1	NM_079422.3	c.3+64T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000352451.4	c.133-963T>C		intron_variant		1	NM_079420.3
MYL1	ENST00000341685.8	c.3+64T>C		intron_variant		1		P1
MYL1	ENST00000484290.1	n.74+64T>C		intron_variant, non_coding_transcript_variant		5
MYL1	ENST00000496436.5	n.74+64T>C		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0778 AC: 11837 AN: 152120 Hom.: 514 Cov.: 32

Gnomad AFR AF: 0.0602

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0691

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.000963

Gnomad SAS AF: 0.0842

Gnomad FIN AF: 0.0435

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0976

Gnomad OTH AF: 0.0789

GnomAD4 exome AF: 0.0941 AC: 127060 AN: 1349646 Hom.: 6756 AF XY: 0.0945 AC XY: 63831 AN XY: 675156

Gnomad4 AFR exome AF: 0.0609

Gnomad4 AMR exome AF: 0.0593

Gnomad4 ASJ exome AF: 0.136

Gnomad4 EAS exome AF: 0.000318

Gnomad4 SAS exome AF: 0.0813

Gnomad4 FIN exome AF: 0.0439

Gnomad4 NFE exome AF: 0.102

Gnomad4 OTH exome AF: 0.0977

GnomAD4 genome AF: 0.0778 AC: 11841 AN: 152238 Hom.: 517 Cov.: 32 AF XY: 0.0747 AC XY: 5560 AN XY: 74434

Gnomad4 AFR AF: 0.0602

Gnomad4 AMR AF: 0.0691

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.000966

Gnomad4 SAS AF: 0.0846

Gnomad4 FIN AF: 0.0435

Gnomad4 NFE AF: 0.0976

Gnomad4 OTH AF: 0.0776

Alfa AF: 0.0874 Hom.: 130

Bravo AF: 0.0794

Asia WGS AF: 0.0320 AC: 113 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 16, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.090
Dann	Benign	0.48

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: rs13025700; hg19: chr2-211168202; COSMIC: COSV104420140;