2-210303622-A-C

Variant summary

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

The ENST00000341685.8(MYL1):c.-78T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.487 in 1,578,092 control chromosomes in the GnomAD database, including 189,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (20857 hom., cov: 31)
  • Exomes 𝑓: 0.48 (168282 hom.)
• Consequence: MYL1 ENST00000341685.8 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.69

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=-0.54).
• BP6: Variant 2-210303622-A-C is Benign according to our data. Variant chr2-210303622-A-C is described in ClinVar as [Benign]. Clinvar id is 1239346.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3	c.133-1107T>G		intron_variant		ENST00000352451.4
MYL1	NM_079422.3			upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000341685.8	c.-78T>G		5_prime_UTR_variant	1/7	1		P1
MYL1	ENST00000352451.4	c.133-1107T>G		intron_variant		1	NM_079420.3
MYL1	ENST00000484290.1			upstream_gene_variant		5
MYL1	ENST00000496436.5			upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79238 AN: 151872 Hom.: 20808 Cov.: 31

Gnomad AFR AF: 0.583

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.585

Gnomad ASJ AF: 0.595

Gnomad EAS AF: 0.452

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.472

Gnomad OTH AF: 0.528

GnomAD4 exome AF: 0.483 AC: 688522 AN: 1426104 Hom.: 168282 Cov.: 30 AF XY: 0.485 AC XY: 343498 AN XY: 708948

Gnomad4 AFR exome AF: 0.590

Gnomad4 AMR exome AF: 0.629

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.442

Gnomad4 SAS exome AF: 0.544

Gnomad4 FIN exome AF: 0.493

Gnomad4 NFE exome AF: 0.467

Gnomad4 OTH exome AF: 0.506

GnomAD4 genome AF: 0.522 AC: 79346 AN: 151988 Hom.: 20857 Cov.: 31 AF XY: 0.527 AC XY: 39119 AN XY: 74266

Gnomad4 AFR AF: 0.584

Gnomad4 AMR AF: 0.586

Gnomad4 ASJ AF: 0.595

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.549

Gnomad4 FIN AF: 0.503

Gnomad4 NFE AF: 0.472

Gnomad4 OTH AF: 0.527

Alfa AF: 0.452 Hom.: 4111

Bravo AF: 0.528

Asia WGS AF: 0.541 AC: 1880 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	-0.54
Cadd	Benign	16
Dann	Benign	0.78

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: rs12469767; hg19: chr2-211168346; COSMIC: COSV58977249; COSMIC: COSV58977249;