2-210294131-T-C

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.478+114A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,130,324 control chromosomes in the GnomAD database, including 7,286 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.12 (1421 hom., cov: 32)
  • Exomes 𝑓: 0.10 (5865 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.572

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=-0.84).
• BP6: Variant 2-210294131-T-C is Benign according to our data. Variant chr2-210294131-T-C is described in ClinVar as [Benign]. Clinvar id is 1227782.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3	c.478+114A>G		intron_variant		ENST00000352451.4
MYL1	NM_079422.3	c.346+114A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000352451.4	c.478+114A>G		intron_variant		1	NM_079420.3
MYL1	ENST00000341685.8	c.346+114A>G		intron_variant		1		P1
MYL1	ENST00000484290.1	n.609+114A>G		intron_variant, non_coding_transcript_variant		5
MYL1	ENST00000496436.5	n.581+114A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18697 AN: 152138 Hom.: 1400 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.0296

Gnomad AMR AF: 0.0854

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.00557

Gnomad SAS AF: 0.133

Gnomad FIN AF: 0.0442

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.101 AC: 98631 AN: 978068 Hom.: 5865 AF XY: 0.102 AC XY: 49119 AN XY: 482848

Gnomad4 AFR exome AF: 0.211

Gnomad4 AMR exome AF: 0.0801

Gnomad4 ASJ exome AF: 0.137

Gnomad4 EAS exome AF: 0.00261

Gnomad4 SAS exome AF: 0.120

Gnomad4 FIN exome AF: 0.0447

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.111

GnomAD4 genome AF: 0.123 AC: 18757 AN: 152256 Hom.: 1421 Cov.: 32 AF XY: 0.120 AC XY: 8945 AN XY: 74456

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0853

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.00559

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0442

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.110

Alfa AF: 0.112 Hom.: 148

Bravo AF: 0.130

Asia WGS AF: 0.0740 AC: 259 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 13, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.2
Dann	Benign	0.56

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: rs71350737; hg19: chr2-211158855; COSMIC: COSV104420139;