16-15745246-G-T

Variant names:

Variant summary

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

The NM_002474.3(MYH11):c.2412-9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,610,528 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 38 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 33 hom. )

Consequence

MYH11
NM_002474.3 intron

Scores

Splicing: ADA: 0.0001252

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.414

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:

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=-0.9).

BP6

Variant 16-15745246-G-T is Benign according to our data. Variant chr16-15745246-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 36617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr16-15745246-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0123 (1874/152190) while in subpopulation AFR AF= 0.0428 (1779/41524). AF 95% confidence interval is 0.0412. There are 38 homozygotes in gnomad4. There are 879 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 38 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3 link	c.2412-9C>A	intron_variant	Intron 19 of 40	ENST00000300036.6	NP_002465.1	P35749-1A0A024QZJ4
MYH11	NM_001040113.2 link	c.2433-9C>A	intron_variant	Intron 20 of 42	ENST00000452625.7	NP_001035202.1	P35749-3
MYH11	NM_001040114.2 link	c.2433-9C>A	intron_variant	Intron 20 of 41		NP_001035203.1	P35749-2
MYH11	NM_022844.3 link	c.2412-9C>A	intron_variant	Intron 19 of 41		NP_074035.1	P35749-4A0A024QZJ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6 link	c.2412-9C>A		intron_variant	Intron 19 of 40	1	NM_002474.3	ENSP00000300036.5		P35749-1
MYH11	ENST00000452625.7 link	c.2433-9C>A		intron_variant	Intron 20 of 42	1	NM_001040113.2	ENSP00000407821.2		P35749-3

Frequencies

GnomAD3 genomes

AF:

0.0123

AC:

1872

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0429

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00337

AC:

844

AN:

250446

Hom.:

AF XY:

0.00246

AC XY:

333

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.0437

Gnomad AMR exome

AF:

0.00188

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00332

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00131

AC:

1904

AN:

1458338

Hom.:

Cov.:

AF XY:

0.00108

AC XY:

781

AN XY:

725652

show subpopulations

Gnomad4 AFR exome

AF:

0.0439

Gnomad4 AMR exome

AF:

0.00197

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00343

Gnomad4 SAS exome

AF:

0.000139

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000316

Gnomad4 OTH exome

AF:

0.00262

GnomAD4 genome

AF:

0.0123

AC:

1874

AN:

152190

Hom.:

Cov.:

AF XY:

0.0118

AC XY:

879

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.0428

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00328

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.000672

Hom.:

Bravo

AF:

0.0137

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 15, 2013

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:2

Mar 21, 2023

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 02, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aortic aneurysm, familial thoracic 4

Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Familial aortopathy

Benign:1

Sep 17, 2014

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:1

Oct 21, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Connective tissue disorder

Benign:1

Nov 01, 2016

Center for Human Genetics, Inc, Center for Human Genetics, Inc

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.2

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00013

dbscSNV1_RF

Benign

0.010

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