Variant rs146859926 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002476.2(MYL4):c.488-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,614,020 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0042 ( 21 hom. )

Consequence

MYL4
NM_002476.2 splice_region, intron

Scores

Splicing: ADA: 0.00004702

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.03

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-47222376-G-A is Benign according to our data. Variant chr17-47222376-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 476206.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-47222376-G-A is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0033 (502/152256) while in subpopulation NFE AF= 0.00434 (295/68020). AF 95% confidence interval is 0.00393. There are 0 homozygotes in gnomad4. There are 240 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 502 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL4	NM_002476.2 linkuse as main transcript	c.488-4G>A		splice_region_variant, intron_variant		ENST00000393450.5	NP_002467.1	P12829

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL4	ENST00000393450.5 linkuse as main transcript	c.488-4G>A		splice_region_variant, intron_variant		1	NM_002476.2	ENSP00000377096.1		P12829

Frequencies

GnomAD3 genomes

AF:

0.00330

AC:

502

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00138

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.000851

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00979

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00434

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00357

AC:

898

AN:

251430

Hom.:

AF XY:

0.00352

AC XY:

478

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.000868

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000817

Gnomad FIN exome

AF:

0.00795

Gnomad NFE exome

AF:

0.00556

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00421

AC:

6148

AN:

1461764

Hom.:

Cov.:

AF XY:

0.00413

AC XY:

3002

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.000926

Gnomad4 AMR exome

AF:

0.000805

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00103

Gnomad4 FIN exome

AF:

0.00867

Gnomad4 NFE exome

AF:

0.00481

Gnomad4 OTH exome

AF:

0.00282

GnomAD4 genome

AF:

0.00330

AC:

502

AN:

152256

Hom.:

Cov.:

AF XY:

0.00322

AC XY:

240

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.00137

Gnomad4 AMR

AF:

0.000850

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00979

Gnomad4 NFE

AF:

0.00434

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00354

Hom.:

Bravo

AF:

0.00274

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00403

EpiControl

AF:

0.00350

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 25, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Sep 01, 2024	MYL4: BP4, BS2 -

Atrial fibrillation, familial, 18

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.98

DANN

Benign

0.71

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000047

dbscSNV1_RF

Benign

0.0020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over