rs12469767

Variant names:

• chr2-210303622-A-C
• rs12469767
• ENST00000341685.8:c.-78T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-210303622-A-C
• chr2-210303622-A-G
• chr2-210303622-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.69
• Publications: 10 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=-0.54).
• BP6: Variant 2-210303622-A-C is Benign according to our data. Variant chr2-210303622-A-C is described in ClinVar as Benign. ClinVar VariationId is 1239346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341685.8. 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.133-1107T>G		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.-78T>G		upstream_gene	N/A	NP_524146.1	P05976-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL1	ENST00000341685.8	TSL:1	c.-78T>G		5_prime_UTR	Exon 1 of 7	ENSP00000343321.4	P05976-2
	MYL1	ENST00000352451.4	TSL:1 MANE Select	c.133-1107T>G		intron	N/A	ENSP00000307280.4	P05976-1
	MYL1	ENST00000957378.1		c.133-1107T>G		intron	N/A	ENSP00000627437.1

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

African (AFR) AF: 0.590 AC: 18506 AN: 31378

American (AMR) AF: 0.629 AC: 23774 AN: 37786

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 13856 AN: 24330

East Asian (EAS) AF: 0.442 AC: 16893 AN: 38242

South Asian (SAS) AF: 0.544 AC: 43994 AN: 80880

European-Finnish (FIN) AF: 0.493 AC: 25932 AN: 52604

Middle Eastern (MID) AF: 0.644 AC: 3597 AN: 5586

European-Non Finnish (NFE) AF: 0.467 AC: 512243 AN: 1096546

Other (OTH) AF: 0.506 AC: 29727 AN: 58752

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

African (AFR) AF: 0.584 AC: 24181 AN: 41438

American (AMR) AF: 0.586 AC: 8943 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 2065 AN: 3470

East Asian (EAS) AF: 0.452 AC: 2325 AN: 5146

South Asian (SAS) AF: 0.549 AC: 2638 AN: 4804

European-Finnish (FIN) AF: 0.503 AC: 5317 AN: 10562

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.472 AC: 32076 AN: 67988

Other (OTH) AF: 0.527 AC: 1114 AN: 2112

Alfa AF: 0.467 Hom.: 6728

Bravo AF: 0.528

Asia WGS AF: 0.541 AC: 1880 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	-0.54
CADD	Benign	16
DANN	Benign	0.78
PhyloP100		1.7
PromoterAI		-0.019	Neutral
Mutation Taster		=284/16	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: rs12469767; hg19: chr2-211168346; COSMIC: COSV58977249; COSMIC: COSV58977249;