rs6498573

Positions:

• chr16-15785516-C-T

Variant summary

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

The NM_002474.3(MYH11):​c.633+1114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 151,550 control chromosomes in the GnomAD database, including 1,969 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 0.15 (1969 hom., cov: 29)
  • Exomes 𝑓: 0.13 (0 hom.)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH11	NM_002474.3	c.633+1114G>A		intron_variant		ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.634-798G>A		intron_variant		ENST00000452625.7	NP_001035202.1
MYH11	NM_001040114.2	c.634-798G>A		intron_variant			NP_001035203.1
MYH11	NM_022844.3	c.633+1114G>A		intron_variant			NP_074035.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.633+1114G>A		intron_variant		1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.634-798G>A		intron_variant		1	NM_001040113.2	ENSP00000407821.2

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22825 AN: 151424 Hom.: 1964 Cov.: 29

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.220

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.310

Gnomad FIN AF: 0.0853

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.157

GnomAD4 exome AF: 0.125 AC: 1 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.125 AC XY: 1 AN XY: 8

Gnomad4 NFE exome AF: 0.167

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.151 AC: 22862 AN: 151542 Hom.: 1969 Cov.: 29 AF XY: 0.155 AC XY: 11470 AN XY: 74030

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.220

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.0853

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.158

Alfa AF: 0.139 Hom.: 3078

Bravo AF: 0.157

Asia WGS AF: 0.311 AC: 1079 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.54
DANN	Benign	0.48

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: rs6498573; hg19: chr16-15879373;