16-15788110-C-T

Variant names:

• chr16-15788110-C-T
• rs17213965
• NM_002474.3:c.531-1378G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002474.3(MYH11):​c.531-1378G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.24 (1280 hom., cov: 8)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268
• Publications: 9 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.269 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.531-1378G>A		intron_variant	Intron 4 of 40	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.531-1378G>A		intron_variant	Intron 4 of 42	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.531-1378G>A		intron_variant	Intron 4 of 41		NP_001035203.1
MYH11	NM_022844.3	c.531-1378G>A		intron_variant	Intron 4 of 41		NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.531-1378G>A		intron_variant	Intron 4 of 40	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.531-1378G>A		intron_variant	Intron 4 of 42	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes AF: 0.241 AC: 15906 AN: 65896 Hom.: 1276 Cov.: 8

Gnomad AFR AF: 0.245

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.279

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.236

Gnomad OTH AF: 0.197

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

GnomAD4 genome AF: 0.241 AC: 15919 AN: 65928 Hom.: 1280 Cov.: 8 AF XY: 0.244 AC XY: 7634 AN XY: 31344

African (AFR) AF: 0.245 AC: 4618 AN: 18852

American (AMR) AF: 0.280 AC: 1628 AN: 5808

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 301 AN: 1612

East Asian (EAS) AF: 0.0647 AC: 77 AN: 1190

South Asian (SAS) AF: 0.233 AC: 327 AN: 1404

European-Finnish (FIN) AF: 0.310 AC: 1136 AN: 3668

Middle Eastern (MID) AF: 0.189 AC: 17 AN: 90

European-Non Finnish (NFE) AF: 0.236 AC: 7601 AN: 32204

Other (OTH) AF: 0.195 AC: 169 AN: 868

Alfa AF: 0.133 Hom.: 1681

Bravo AF: 0.137

Asia WGS AF: 0.0760 AC: 259 AN: 3410

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.55
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17213965; hg19: chr16-15881967;