rs2272556

chr16-15735679-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_002474.3(MYH11):c.3294-101C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0154 in 1,139,660 control chromosomes in the GnomAD database, including 545 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (75 hom., cov: 32)
  • Exomes 𝑓: 0.016 (470 hom.)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.13

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BP6: Variant 16-15735679-G-C is Benign according to our data. Variant chr16-15735679-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 674681.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH11	NM_001040113.2	c.3315-101C>G		intron_variant		ENST00000452625.7
MYH11	NM_002474.3	c.3294-101C>G		intron_variant		ENST00000300036.6
MYH11	NM_001040114.2	c.3315-101C>G		intron_variant
MYH11	NM_022844.3	c.3294-101C>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH11	ENST00000300036.6	c.3294-101C>G		intron_variant		1	NM_002474.3	P3
MYH11	ENST00000452625.7	c.3315-101C>G		intron_variant		1	NM_001040113.2

Frequencies

GnomAD3 genomes AF: 0.0144 AC: 2185 AN: 152222 Hom.: 77 Cov.: 32

Gnomad AFR AF: 0.00383

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00792

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.0151

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00895

Gnomad OTH AF: 0.0181

GnomAD4 exome AF: 0.0155 AC: 15326 AN: 987320 Hom.: 470 AF XY: 0.0164 AC XY: 8379 AN XY: 509576

Gnomad4 AFR exome AF: 0.00245

Gnomad4 AMR exome AF: 0.00508

Gnomad4 ASJ exome AF: 0.0182

Gnomad4 EAS exome AF: 0.127

Gnomad4 SAS exome AF: 0.0378

Gnomad4 FIN exome AF: 0.0137

Gnomad4 NFE exome AF: 0.00815

Gnomad4 OTH exome AF: 0.0189

GnomAD4 genome AF: 0.0143 AC: 2181 AN: 152340 Hom.: 75 Cov.: 32 AF XY: 0.0154 AC XY: 1148 AN XY: 74486

Gnomad4 AFR AF: 0.00382

Gnomad4 AMR AF: 0.00791

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.0151

Gnomad4 NFE AF: 0.00895

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00836 Hom.: 2

Bravo AF: 0.0128

Asia WGS AF: 0.0930 AC: 323 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 16, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.022
Dann	Benign	0.64

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: rs2272556; hg19: chr16-15829536; COSMIC: COSV55552625; COSMIC: COSV55552625;