rs881803

Variant names:

• chr16-15708477-C-T
• rs881803
• NM_002474.3:c.5787-4354G>A

Variant summary

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

The NM_002474.3(MYH11):​c.5787-4354G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 151,938 control chromosomes in the GnomAD database, including 26,992 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 0.58 (26992 hom., cov: 32)
• Consequence: MYH11 NM_002474.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.17

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]

NDE1 (HGNC:17619): (nudE neurodevelopment protein 1) This gene encodes a member of the nuclear distribution E (NudE) family of proteins. The encoded protein is localized at the centrosome and interacts with other centrosome components as part of a multiprotein complex that regulates dynein function. This protein plays an essential role in microtubule organization, mitosis and neuronal migration. Mutations in this gene cause lissencephaly 4, a disorder characterized by lissencephaly, severe brain atrophy, microcephaly, and severe cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH11	NM_002474.3	c.5787-4354G>A		intron_variant	Intron 40 of 40	ENST00000300036.6	NP_002465.1
MYH11	NM_001040113.2	c.*8+326G>A		intron_variant	Intron 42 of 42	ENST00000452625.7	NP_001035202.1
NDE1	NM_017668.3	c.947+11617C>T		intron_variant	Intron 8 of 8	ENST00000396354.6	NP_060138.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH11	ENST00000300036.6	c.5787-4354G>A		intron_variant	Intron 40 of 40	1	NM_002474.3	ENSP00000300036.5
MYH11	ENST00000452625.7	c.*8+326G>A		intron_variant	Intron 42 of 42	1	NM_001040113.2	ENSP00000407821.2
NDE1	ENST00000396354.6	c.947+11617C>T		intron_variant	Intron 8 of 8	1	NM_017668.3	ENSP00000379642.1

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88599 AN: 151820 Hom.: 26988 Cov.: 32

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.650

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.736

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.583 AC: 88635 AN: 151938 Hom.: 26992 Cov.: 32 AF XY: 0.584 AC XY: 43366 AN XY: 74256

Gnomad4 AFR AF: 0.382

Gnomad4 AMR AF: 0.658

Gnomad4 ASJ AF: 0.698

Gnomad4 EAS AF: 0.573

Gnomad4 SAS AF: 0.649

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.618

Alfa AF: 0.657 Hom.: 58671

Bravo AF: 0.577

Asia WGS AF: 0.593 AC: 2064 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.4
DANN	Benign	0.71

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: rs881803; hg19: chr16-15802334;