16-15798303-C-T

Variant names:

• chr16-15798303-C-T
• rs17286488
• NM_002474.3:c.530+357G>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.530+357G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0516 in 152,212 control chromosomes in the GnomAD database, including 310 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 0.052 (310 hom., cov: 31)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 6 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.530+357G>A		intron_variant	Intron 4 of 40	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.530+357G>A		intron_variant	Intron 4 of 42	ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.530+357G>A		intron_variant	Intron 4 of 41		NP_001035203.1
MYH11	NM_022844.3	c.530+357G>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.530+357G>A		intron_variant	Intron 4 of 40	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.530+357G>A		intron_variant	Intron 4 of 42	1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes AF: 0.0517 AC: 7864 AN: 152094 Hom.: 310 Cov.: 31

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0359

Gnomad ASJ AF: 0.0735

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0410

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0730

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0516 AC: 7861 AN: 152212 Hom.: 310 Cov.: 31 AF XY: 0.0527 AC XY: 3923 AN XY: 74400

African (AFR) AF: 0.0127 AC: 529 AN: 41546

American (AMR) AF: 0.0359 AC: 549 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0735 AC: 255 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5178

South Asian (SAS) AF: 0.0411 AC: 198 AN: 4822

European-Finnish (FIN) AF: 0.106 AC: 1116 AN: 10572

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4968 AN: 68008

Other (OTH) AF: 0.0445 AC: 94 AN: 2112

Alfa AF: 0.0659 Hom.: 288

Bravo AF: 0.0451

Asia WGS AF: 0.0180 AC: 64 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.034
DANN	Benign	0.19
PhyloP100		-2.1
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: rs17286488; hg19: chr16-15892160;