rs17284809

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002474.3(MYH11):​c.3652-1889G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 151,936 control chromosomes in the GnomAD database, including 131 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 0.035 ( 131 hom., cov: 31)

Consequence

MYH11
NM_002474.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0490
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.84).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0546 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYH11NM_002474.3 linkuse as main transcriptc.3652-1889G>A intron_variant ENST00000300036.6 NP_002465.1 P35749-1A0A024QZJ4
MYH11NM_001040113.2 linkuse as main transcriptc.3673-1889G>A intron_variant ENST00000452625.7 NP_001035202.1 P35749-3
MYH11NM_001040114.2 linkuse as main transcriptc.3673-1889G>A intron_variant NP_001035203.1 P35749-2
MYH11NM_022844.3 linkuse as main transcriptc.3652-1889G>A intron_variant NP_074035.1 P35749-4A0A024QZJ6

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYH11ENST00000300036.6 linkuse as main transcriptc.3652-1889G>A intron_variant 1 NM_002474.3 ENSP00000300036.5 P35749-1
MYH11ENST00000452625.7 linkuse as main transcriptc.3673-1889G>A intron_variant 1 NM_001040113.2 ENSP00000407821.2 P35749-3

Frequencies

GnomAD3 genomes
AF:
0.0346
AC:
5248
AN:
151838
Hom.:
131
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0103
Gnomad AMI
AF:
0.0242
Gnomad AMR
AF:
0.0284
Gnomad ASJ
AF:
0.00518
Gnomad EAS
AF:
0.000970
Gnomad SAS
AF:
0.0164
Gnomad FIN
AF:
0.0369
Gnomad MID
AF:
0.0127
Gnomad NFE
AF:
0.0560
Gnomad OTH
AF:
0.0312
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.0345
AC:
5248
AN:
151936
Hom.:
131
Cov.:
31
AF XY:
0.0318
AC XY:
2358
AN XY:
74260
show subpopulations
Gnomad4 AFR
AF:
0.0102
Gnomad4 AMR
AF:
0.0284
Gnomad4 ASJ
AF:
0.00518
Gnomad4 EAS
AF:
0.000972
Gnomad4 SAS
AF:
0.0165
Gnomad4 FIN
AF:
0.0369
Gnomad4 NFE
AF:
0.0560
Gnomad4 OTH
AF:
0.0309
Alfa
AF:
0.0475
Hom.:
59
Bravo
AF:
0.0329
Asia WGS
AF:
0.0100
AC:
36
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.84
CADD
Benign
4.1
DANN
Benign
0.60

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs17284809; hg19: chr16-15822800; API