rs141564071

Variant names:

• chr16-15798698-AAAG-A
• rs141564071
• NM_002474.3:c.503-14_503-12delCTT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_002474.3(MYH11):​c.503-14_503-12delCTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00614 in 1,613,096 control chromosomes in the GnomAD database, including 423 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.029 (208 hom., cov: 31)
  • Exomes 𝑓: 0.0038 (215 hom.)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 1.96
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 16-15798698-AAAG-A is Benign according to our data. Variant chr16-15798698-AAAG-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 36624.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0947 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002474.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH11	NM_002474.3	MANE Select	c.503-14_503-12delCTT		intron	N/A	NP_002465.1
	MYH11	NM_001040113.2	MANE Plus Clinical	c.503-14_503-12delCTT		intron	N/A	NP_001035202.1
	MYH11	NM_001040114.2		c.503-14_503-12delCTT		intron	N/A	NP_001035203.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH11	ENST00000300036.6	TSL:1 MANE Select	c.503-14_503-12delCTT		intron	N/A	ENSP00000300036.5
	MYH11	ENST00000452625.7	TSL:1 MANE Plus Clinical	c.503-14_503-12delCTT		intron	N/A	ENSP00000407821.2
	MYH11	ENST00000396324.7	TSL:1	c.503-14_503-12delCTT		intron	N/A	ENSP00000379616.3

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4372 AN: 151806 Hom.: 206 Cov.: 31

Gnomad AFR AF: 0.0972

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.00876 AC: 2199 AN: 251078 AF XY: 0.00679

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00490

Gnomad ASJ exome AF: 0.0278

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000757

Gnomad OTH exome AF: 0.00473

GnomAD4 exome AF: 0.00378 AC: 5517 AN: 1461180 Hom.: 215 AF XY: 0.00329 AC XY: 2388 AN XY: 726926

African (AFR) AF: 0.101 AC: 3378 AN: 33302

American (AMR) AF: 0.00558 AC: 249 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 743 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000302 AC: 26 AN: 86138

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00624 AC: 36 AN: 5768

European-Non Finnish (NFE) AF: 0.000487 AC: 541 AN: 1111772

Other (OTH) AF: 0.00901 AC: 544 AN: 60362

GnomAD4 genome AF: 0.0289 AC: 4384 AN: 151916 Hom.: 208 Cov.: 31 AF XY: 0.0274 AC XY: 2035 AN XY: 74266

African (AFR) AF: 0.0972 AC: 4012 AN: 41266

American (AMR) AF: 0.0125 AC: 191 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0271 AC: 94 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000647 AC: 44 AN: 68012

Other (OTH) AF: 0.0199 AC: 42 AN: 2108

Alfa AF: 0.0228 Hom.: 24

Bravo AF: 0.0335

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Aortic aneurysm, familial thoracic 4 (3)
-	-	2	Familial thoracic aortic aneurysm and aortic dissection (2)
-	-	2	not specified (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.0
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: rs141564071; hg19: chr16-15892555;