rs8051319

Variant names:

• chr16-15793091-T-C
• rs8051319
• NM_002474.3:c.530+5569A>G

Variant summary

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

The NM_002474.3(MYH11):​c.530+5569A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 151,834 control chromosomes in the GnomAD database, including 15,959 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 0.44 (15959 hom., cov: 31)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.28
• Publications: 2 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.614 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.530+5569A>G		intron_variant	Intron 4 of 40	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.530+5569A>G		intron_variant	Intron 4 of 42	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.530+5569A>G		intron_variant	Intron 4 of 41		NP_001035203.1
MYH11	NM_022844.3	c.530+5569A>G		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.530+5569A>G		intron_variant	Intron 4 of 40	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.530+5569A>G		intron_variant	Intron 4 of 42	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes AF: 0.442 AC: 67020 AN: 151716 Hom.: 15934 Cov.: 31

Gnomad AFR AF: 0.620

Gnomad AMI AF: 0.281

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.462

Gnomad EAS AF: 0.157

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.410

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

GnomAD4 genome AF: 0.442 AC: 67085 AN: 151834 Hom.: 15959 Cov.: 31 AF XY: 0.439 AC XY: 32597 AN XY: 74212

African (AFR) AF: 0.620 AC: 25646 AN: 41372

American (AMR) AF: 0.317 AC: 4834 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.462 AC: 1605 AN: 3472

East Asian (EAS) AF: 0.157 AC: 807 AN: 5142

South Asian (SAS) AF: 0.332 AC: 1593 AN: 4804

European-Finnish (FIN) AF: 0.428 AC: 4505 AN: 10522

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.395 AC: 26833 AN: 67944

Other (OTH) AF: 0.411 AC: 867 AN: 2110

Alfa AF: 0.463 Hom.: 7963

Bravo AF: 0.441

Asia WGS AF: 0.281 AC: 982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.88
DANN	Benign	0.60
PhyloP100		-2.3
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: rs8051319; hg19: chr16-15886948;