17-47213813-C-T

Variant names:

• chr17-47213813-C-T
• rs143234546
• NM_002476.2:c.150C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_002476.2(MYL4):​c.150C>T​(p.Ala50Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000209 in 1,614,118 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A50A) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00097 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: MYL4 NM_002476.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.03
• Publications: 0 publications found

Genes affected

MYL4 (HGNC:7585): (myosin light chain 4) Myosin is a hexameric ATPase cellular motor protein. It is composed of two myosin heavy chains, two nonphosphorylatable myosin alkali light chains, and two phosphorylatable myosin regulatory light chains. This gene encodes a myosin alkali light chain that is found in embryonic muscle and adult atria. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

MYL4 Gene-Disease associations (from GenCC):

• atrial fibrillation, familial, 18

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 17-47213813-C-T is Benign according to our data. Variant chr17-47213813-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 476198.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000972 (148/152284) while in subpopulation AFR AF = 0.00306 (127/41546). AF 95% confidence interval is 0.00262. There are 0 homozygotes in GnomAd4. There are 60 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 148 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002476.2. 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
	MYL4	NM_002476.2	MANE Select	c.150C>T	p.Ala50Ala	synonymous	Exon 2 of 7	NP_002467.1	P12829
	MYL4	NM_001002841.2		c.150C>T	p.Ala50Ala	synonymous	Exon 3 of 8	NP_001002841.1	P12829

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL4	ENST00000393450.5	TSL:1 MANE Select	c.150C>T	p.Ala50Ala	synonymous	Exon 2 of 7	ENSP00000377096.1	P12829
	MYL4	ENST00000954756.1		c.146C>T	p.Pro49Leu	missense	Exon 2 of 7	ENSP00000624815.1
	MYL4	ENST00000954741.1		c.150C>T	p.Ala50Ala	synonymous	Exon 2 of 7	ENSP00000624800.1

Frequencies

GnomAD3 genomes AF: 0.000933 AC: 142 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00292

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000523

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000306 AC: 77 AN: 251486 AF XY: 0.000228

Gnomad AFR exome AF: 0.00308

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000879

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000129 AC: 189 AN: 1461834 Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 78 AN XY: 727216

African (AFR) AF: 0.00305 AC: 102 AN: 33478

American (AMR) AF: 0.000380 AC: 17 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5768

European-Non Finnish (NFE) AF: 0.0000495 AC: 55 AN: 1111962

Other (OTH) AF: 0.000149 AC: 9 AN: 60394

GnomAD4 genome AF: 0.000972 AC: 148 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.000806 AC XY: 60 AN XY: 74476

African (AFR) AF: 0.00306 AC: 127 AN: 41546

American (AMR) AF: 0.000523 AC: 8 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68024

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.000488 Hom.: 0

Bravo AF: 0.00102

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Atrial fibrillation, familial, 18 (1)
-	-	1	MYL4-related disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	2.2
DANN	Benign	0.75
PhyloP100		-2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs143234546; hg19: chr17-45291179;