2-210294124-T-A

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+121A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00431 in 1,024,164 control chromosomes in the GnomAD database, including 126 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.018 (73 hom., cov: 33)
  • Exomes 𝑓: 0.0020 (53 hom.)
• Consequence: MYL1 NM_079420.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.302

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=-0.78).
• BP6: Variant 2-210294124-T-A is Benign according to our data. Variant chr2-210294124-T-A is described in ClinVar as [Benign]. Clinvar id is 1242873.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0587 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3	c.478+121A>T		intron_variant		ENST00000352451.4
MYL1	NM_079422.3	c.346+121A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000352451.4	c.478+121A>T		intron_variant		1	NM_079420.3
MYL1	ENST00000341685.8	c.346+121A>T		intron_variant		1		P1
MYL1	ENST00000484290.1	n.609+121A>T		intron_variant, non_coding_transcript_variant		5
MYL1	ENST00000496436.5	n.581+121A>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.0178 AC: 2701 AN: 151666 Hom.: 74 Cov.: 33

Gnomad AFR AF: 0.0607

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00913

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000418

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000280

Gnomad OTH AF: 0.0145

GnomAD4 exome AF: 0.00196 AC: 1712 AN: 872380 Hom.: 53 AF XY: 0.00177 AC XY: 765 AN XY: 432358

Gnomad4 AFR exome AF: 0.0663

Gnomad4 AMR exome AF: 0.00497

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000904

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000186

Gnomad4 OTH exome AF: 0.00456

GnomAD4 genome AF: 0.0178 AC: 2706 AN: 151784 Hom.: 73 Cov.: 33 AF XY: 0.0170 AC XY: 1261 AN XY: 74170

Gnomad4 AFR AF: 0.0607

Gnomad4 AMR AF: 0.00906

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000418

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000280

Gnomad4 OTH AF: 0.0143

Alfa AF: 0.0135 Hom.: 6

Bravo AF: 0.0209

Asia WGS AF: 0.00577 AC: 21 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 22, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.4
Dann	Benign	0.74

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: rs13427549; hg19: chr2-211158848; COSMIC: COSV104420149;