16-15745246-G-T

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

2
Splicing: ADA: 0.0001252
2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

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]

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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=-0.9).
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 HGVSp Effect Exon rank MANE Protein UniProt
MYH11NM_002474.3 linkc.2412-9C>A intron_variant Intron 19 of 40 ENST00000300036.6 NP_002465.1 P35749-1A0A024QZJ4
MYH11NM_001040113.2 linkc.2433-9C>A intron_variant Intron 20 of 42 ENST00000452625.7 NP_001035202.1 P35749-3
MYH11NM_001040114.2 linkc.2433-9C>A intron_variant Intron 20 of 41 NP_001035203.1 P35749-2
MYH11NM_022844.3 linkc.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
MYH11ENST00000300036.6 linkc.2412-9C>A intron_variant Intron 19 of 40 1 NM_002474.3 ENSP00000300036.5 P35749-1
MYH11ENST00000452625.7 linkc.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.:
38
Cov.:
32
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.:
14
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.:
33
Cov.:
31
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.:
38
Cov.:
32
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.:
0
Bravo
AF:
0.0137
Asia WGS
AF:
0.00231
AC:
8
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:4
-
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Significance: Benign
Review Status: no assertion criteria provided
Collection Method: clinical testing

- -

-
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 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. -

Familial thoracic aortic aneurysm and aortic dissection Benign:2
Apr 02, 2018
Color Diagnostics, LLC DBA Color Health
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

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

- -

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.

Other links and lift over

dbSNP: rs148682361; hg19: chr16-15839103; API