17-47218137-C-G

Variant names:

• chr17-47218137-C-G
• rs16941671
• NM_002476.2:c.164-1767C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002476.2(MYL4):​c.164-1767C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0822 in 151,602 control chromosomes in the GnomAD database, including 699 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.082 (699 hom., cov: 32)
• Consequence: MYL4 NM_002476.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 3 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.188 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL4	NM_002476.2	c.164-1767C>G		intron_variant	Intron 2 of 6	ENST00000393450.5	NP_002467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL4	ENST00000393450.5	c.164-1767C>G		intron_variant	Intron 2 of 6	1	NM_002476.2	ENSP00000377096.1

Frequencies

GnomAD3 genomes AF: 0.0823 AC: 12464 AN: 151514 Hom.: 701 Cov.: 32

Gnomad AFR AF: 0.0258

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.0927

Gnomad ASJ AF: 0.0812

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.188

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.0839

Gnomad NFE AF: 0.0989

Gnomad OTH AF: 0.0817

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0822 AC: 12462 AN: 151602 Hom.: 699 Cov.: 32 AF XY: 0.0851 AC XY: 6303 AN XY: 74028

African (AFR) AF: 0.0258 AC: 1066 AN: 41308

American (AMR) AF: 0.0926 AC: 1411 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.0812 AC: 282 AN: 3472

East Asian (EAS) AF: 0.198 AC: 1023 AN: 5160

South Asian (SAS) AF: 0.188 AC: 901 AN: 4798

European-Finnish (FIN) AF: 0.0721 AC: 750 AN: 10404

Middle Eastern (MID) AF: 0.0903 AC: 26 AN: 288

European-Non Finnish (NFE) AF: 0.0990 AC: 6722 AN: 67930

Other (OTH) AF: 0.0815 AC: 171 AN: 2098

Alfa AF: 0.0915 Hom.: 94

Bravo AF: 0.0761

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.8
DANN	Benign	0.51
PhyloP100		0.58
Mutation Taster		=100/0	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: rs16941671; hg19: chr17-45295503;