rs215590

chr16-15833734-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_002474.3(MYH11):c.345+4174G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,990 control chromosomes in the GnomAD database, including 9,298 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 0.34 (9298 hom., cov: 31)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.520

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.414 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH11	NM_001040113.2	c.345+4174G>T		intron_variant		ENST00000452625.7
MYH11	NM_002474.3	c.345+4174G>T		intron_variant		ENST00000300036.6
MYH11	NM_001040114.2	c.345+4174G>T		intron_variant
MYH11	NM_022844.3	c.345+4174G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH11	ENST00000300036.6	c.345+4174G>T		intron_variant		1	NM_002474.3	P3
MYH11	ENST00000452625.7	c.345+4174G>T		intron_variant		1	NM_001040113.2

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51023 AN: 151872 Hom.: 9296 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.402

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.136

Gnomad SAS AF: 0.304

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.392

Gnomad OTH AF: 0.347

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

GnomAD4 genome AF: 0.336 AC: 51049 AN: 151990 Hom.: 9298 Cov.: 31 AF XY: 0.336 AC XY: 24976 AN XY: 74248

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.374

Gnomad4 EAS AF: 0.136

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.392

Gnomad4 OTH AF: 0.348

Alfa AF: 0.377 Hom.: 8009

Bravo AF: 0.334

Asia WGS AF: 0.222 AC: 772 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	5.2
Dann	Benign	0.81

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

LitVar

Other links and lift over

dbSNP: rs215590; hg19: chr16-15927591;