Genetic Variant NM_002474.3:c.-18+1151C>T (chr16-15855790-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002474.3(MYH11):c.-18+1151C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.192 in 152,080 control chromosomes in the GnomAD database, including 3,439 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 0.19 ( 3439 hom., cov: 32)

Consequence

MYH11
NM_002474.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.708

Publications

7 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=-0.87).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
MYH11	NM_002474.3 link	c.-18+1151C>T	intron_variant	Intron 1 of 40	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2 link	c.-18+1151C>T	intron_variant	Intron 1 of 42	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2 link	c.-18+1151C>T	intron_variant	Intron 1 of 41		NP_001035203.1
MYH11	NM_022844.3 link	c.-18+1151C>T	intron_variant	Intron 1 of 41		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6 link	c.-18+1151C>T		intron_variant	Intron 1 of 40	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7 link	c.-18+1151C>T		intron_variant	Intron 1 of 42	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes

AF:

0.192

AC:

29200

AN:

151962

Hom.:

3433

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0648

Gnomad AMI

AF:

0.166

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.428

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.200

Gnomad MID

AF:

0.222

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.220

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.192

AC:

29206

AN:

152080

Hom.:

3439

Cov.:

AF XY:

0.190

AC XY:

14135

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.0646

AC:

2681

AN:

41500

American (AMR)

AF:

0.186

AC:

2838

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

756

AN:

3464

East Asian (EAS)

AF:

0.429

AC:

2214

AN:

5166

South Asian (SAS)

AF:

0.310

AC:

1495

AN:

4828

European-Finnish (FIN)

AF:

0.200

AC:

2112

AN:

10550

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.242

AC:

16434

AN:

67976

Other (OTH)

AF:

0.218

AC:

461

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1150

2300

3451

4601

5751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

328

656

984

1312

1640

<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:

0.212

Hom.:

1610

Bravo

AF:

0.185

Asia WGS

AF:

0.351

AC:

1221

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

5.0

(source)

DANN

Benign

0.83

PhyloP100

0.71

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