16-15759739-C-G

Position:

chr16-15759739-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002474.3(MYH11):c.1249-11G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.402 in 1,613,218 control chromosomes in the GnomAD database, including 136,001 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 18149 hom., cov: 32)

Exomes 𝑓: 0.39 ( 117852 hom. )

Consequence

MYH11
NM_002474.3 intron

Scores

Splicing: ADA: 0.00003464

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -0.720

Variant links:

Genes affected

MYH11 (HGNC:7569): (myosin heavy chain 11) The protein encoded by this gene is a smooth muscle myosin belonging to the myosin heavy chain family. The gene product is a subunit of a hexameric protein that consists of two heavy chain subunits and two pairs of non-identical light chain subunits. It functions as a major contractile protein, converting chemical energy into mechanical energy through the hydrolysis of ATP. A chromosomal rearrangement involving this gene is associated with acute myeloid leukemia of the M4Eo subtype. Mutations in this gene are associated with visceral myopathy, megacystis-microcolon-intestinal hypoperistalsis syndrome 2, and familial thoracic aortic aneurysm 4. [provided by RefSeq, May 2022]

MYH11 links:

MYH11 (HGNC:):

MYH11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 16-15759739-C-G is Benign according to our data. Variant chr16-15759739-C-G is described in ClinVar as [Benign]. Clinvar id is 138371.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-15759739-C-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.665 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH11	NM_002474.3 linkuse as main transcript	c.1249-11G>C		intron_variant		ENST00000300036.6	NP_002465.1	P35749-1A0A024QZJ4
MYH11	NM_001040113.2 linkuse as main transcript	c.1270-11G>C		intron_variant		ENST00000452625.7	NP_001035202.1	P35749-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6 linkuse as main transcript	c.1249-11G>C		intron_variant		1	NM_002474.3	ENSP00000300036.5		P35749-1
MYH11	ENST00000452625.7 linkuse as main transcript	c.1270-11G>C		intron_variant		1	NM_001040113.2	ENSP00000407821.2		P35749-3

Frequencies

GnomAD3 genomes

AF:

0.467

AC:

70999

AN:

151934

Hom.:

18110

Cov.:

show subpopulations

Gnomad AFR

AF:

0.671

Gnomad AMI

AF:

0.241

Gnomad AMR

AF:

0.389

Gnomad ASJ

AF:

0.378

Gnomad EAS

AF:

0.682

Gnomad SAS

AF:

0.430

Gnomad FIN

AF:

0.339

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.438

GnomAD3 exomes

AF:

0.411

AC:

103052

AN:

250574

Hom.:

22834

AF XY:

0.405

AC XY:

54941

AN XY:

135494

show subpopulations

Gnomad AFR exome

AF:

0.677

Gnomad AMR exome

AF:

0.341

Gnomad ASJ exome

AF:

0.382

Gnomad EAS exome

AF:

0.694

Gnomad SAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.346

Gnomad NFE exome

AF:

0.366

Gnomad OTH exome

AF:

0.376

GnomAD4 exome

AF:

0.395

AC:

576816

AN:

1461166

Hom.:

117852

Cov.:

AF XY:

0.394

AC XY:

286661

AN XY:

726898

show subpopulations

Gnomad4 AFR exome

AF:

0.674

Gnomad4 AMR exome

AF:

0.345

Gnomad4 ASJ exome

AF:

0.383

Gnomad4 EAS exome

AF:

0.680

Gnomad4 SAS exome

AF:

0.408

Gnomad4 FIN exome

AF:

0.339

Gnomad4 NFE exome

AF:

0.379

Gnomad4 OTH exome

AF:

0.419

GnomAD4 genome

AF:

0.468

AC:

71095

AN:

152052

Hom.:

18149

Cov.:

AF XY:

0.465

AC XY:

34546

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.671

Gnomad4 AMR

AF:

0.389

Gnomad4 ASJ

AF:

0.378

Gnomad4 EAS

AF:

0.681

Gnomad4 SAS

AF:

0.431

Gnomad4 FIN

AF:

0.339

Gnomad4 NFE

AF:

0.376

Gnomad4 OTH

AF:

0.442

Alfa

AF:

0.410

Hom.:

2452

Bravo

AF:

0.479

Asia WGS

AF:

0.546

AC:

1899

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 04, 2013	1270-11G>C in intron 12 of MYH11: This variant is not expected to have clinical significance because it has been identified in 37.3% (3209/8600) of European Ame rican chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2280764). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 05, 2012	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Aortic aneurysm, familial thoracic 4

Benign:3

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Visceral myopathy 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Megacystis-microcolon-intestinal hypoperistalsis syndrome 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Benign, criteria provided, single submitter

clinical testing

Color Diagnostics, LLC DBA Color Health

Mar 19, 2018

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.2

DANN

Benign

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000035

dbscSNV1_RF

Benign

0.0

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