rs2075514

chr16-15778752-A-G

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.790+28T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 1,611,568 control chromosomes in the GnomAD database, including 31,962 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.19 (2971 hom., cov: 31)
  • Exomes 𝑓: 0.20 (28991 hom.)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.90

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=-0.9).
• BP6: Variant 16-15778752-A-G is Benign according to our data. Variant chr16-15778752-A-G is described in ClinVar as [Benign]. Clinvar id is 671006.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH11	NM_001040113.2	c.811+28T>C		intron_variant		ENST00000452625.7
MYH11	NM_002474.3	c.790+28T>C		intron_variant		ENST00000300036.6
MYH11	NM_001040114.2	c.811+28T>C		intron_variant
MYH11	NM_022844.3	c.790+28T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH11	ENST00000300036.6	c.790+28T>C		intron_variant		1	NM_002474.3	P3
MYH11	ENST00000452625.7	c.811+28T>C		intron_variant		1	NM_001040113.2

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29523 AN: 151880 Hom.: 2970 Cov.: 31

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.194

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.181

Gnomad EAS AF: 0.293

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.193

GnomAD3 exomes AF: 0.194 AC: 48864 AN: 251438 Hom.: 5161 AF XY: 0.196 AC XY: 26647 AN XY: 135892

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.183

Gnomad EAS exome AF: 0.299

Gnomad SAS exome AF: 0.152

Gnomad FIN exome AF: 0.265

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.201

GnomAD4 exome AF: 0.197 AC: 287100 AN: 1459570 Hom.: 28991 Cov.: 31 AF XY: 0.196 AC XY: 142421 AN XY: 726280

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.154

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.199

Gnomad4 OTH exome AF: 0.193

GnomAD4 genome AF: 0.194 AC: 29547 AN: 151998 Hom.: 2971 Cov.: 31 AF XY: 0.195 AC XY: 14469 AN XY: 74274

Gnomad4 AFR AF: 0.173

Gnomad4 AMR AF: 0.153

Gnomad4 ASJ AF: 0.181

Gnomad4 EAS AF: 0.293

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.268

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.198

Alfa AF: 0.199 Hom.: 1612

Bravo AF: 0.187

Asia WGS AF: 0.207 AC: 718 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 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	-0.90
Cadd	Benign	0.015
Dann	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2075514; hg19: chr16-15872609; COSMIC: COSV55541857;