dbSNP rs6498573: MYH11:n.1852G>A (chr16-15785516-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000571505.1(MYH11):n.1852G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,550 control chromosomes in the GnomAD database, including 1,969 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 0.15 ( 1969 hom., cov: 29)

Exomes 𝑓: 0.13 ( 0 hom. )

Consequence

MYH11
ENST00000571505.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.12

Publications

13 publications found

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 Gene-Disease associations (from GenCC):

familial thoracic aortic aneurysm and aortic dissection
Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
aortic aneurysm, familial thoracic 4
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
megacystis-microcolon-intestinal hypoperistalsis syndrome 2
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae)
megacystis-microcolon-intestinal hypoperistalsis syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
visceral myopathy 2
Inheritance: AR, AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

MYH11 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MYH11	NM_002474.3 link	c.633+1114G>A	intron_variant	Intron 5 of 40	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2 link	c.634-798G>A	intron_variant	Intron 5 of 42	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2 link	c.634-798G>A	intron_variant	Intron 5 of 41		NP_001035203.1
MYH11	NM_022844.3 link	c.633+1114G>A	intron_variant	Intron 5 of 41		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6 link	c.633+1114G>A		intron_variant	Intron 5 of 40	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7 link	c.634-798G>A		intron_variant	Intron 5 of 42	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

22825

AN:

151424

Hom.:

1964

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.315

Gnomad AMR

AF:

0.220

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.310

Gnomad FIN

AF:

0.0853

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.130

Gnomad OTH

AF:

0.157

GnomAD4 exome

AF:

0.125

AC:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.151

AC:

22862

AN:

151542

Hom.:

1969

Cov.:

AF XY:

0.155

AC XY:

11470

AN XY:

74030

show subpopulations

African (AFR)

AF:

0.141

AC:

5816

AN:

41250

American (AMR)

AF:

0.220

AC:

3344

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

406

AN:

3462

East Asian (EAS)

AF:

0.276

AC:

1419

AN:

5148

South Asian (SAS)

AF:

0.310

AC:

1481

AN:

4780

European-Finnish (FIN)

AF:

0.0853

AC:

898

AN:

10532

Middle Eastern (MID)

AF:

0.130

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.130

AC:

8844

AN:

67908

Other (OTH)

AF:

0.158

AC:

329

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

936

1872

2809

3745

4681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

262

524

786

1048

1310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.138

Hom.:

6312

Bravo

AF:

0.157

Asia WGS

AF:

0.311

AC:

1079

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.54

(source)

DANN

Benign

0.48

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over