rs766083

Variant summary

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

The NM_013451.4(MYOF):​c.236+8403A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 151,940 control chromosomes in the GnomAD database, including 30,470 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 0.62 ( 30470 hom., cov: 30)

Consequence

MYOF
NM_013451.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.67
Variant links:
Genes affected
MYOF (HGNC:3656): (myoferlin) Mutations in dysferlin, a protein associated with the plasma membrane, can cause muscle weakness that affects both proximal and distal muscles. The protein encoded by this gene is a type II membrane protein that is structurally similar to dysferlin. It is a member of the ferlin family and associates with both plasma and nuclear membranes. The protein contains C2 domains that play a role in calcium-mediated membrane fusion events, suggesting that it may be involved in membrane regeneration and repair. Two transcript variants encoding different isoforms have been found for this gene. Other possible variants have been detected, but their full-length nature has not been determined. [provided by RefSeq, Dec 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.91).
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MYOFNM_013451.4 linkuse as main transcriptc.236+8403A>G intron_variant ENST00000359263.9 NP_038479.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYOFENST00000359263.9 linkuse as main transcriptc.236+8403A>G intron_variant 1 NM_013451.4 ENSP00000352208 P1Q9NZM1-1

Frequencies

GnomAD3 genomes
AF:
0.619
AC:
93924
AN:
151822
Hom.:
30460
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.413
Gnomad AMI
AF:
0.759
Gnomad AMR
AF:
0.646
Gnomad ASJ
AF:
0.554
Gnomad EAS
AF:
0.768
Gnomad SAS
AF:
0.642
Gnomad FIN
AF:
0.824
Gnomad MID
AF:
0.598
Gnomad NFE
AF:
0.694
Gnomad OTH
AF:
0.593
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.618
AC:
93961
AN:
151940
Hom.:
30470
Cov.:
30
AF XY:
0.624
AC XY:
46316
AN XY:
74228
show subpopulations
Gnomad4 AFR
AF:
0.413
Gnomad4 AMR
AF:
0.646
Gnomad4 ASJ
AF:
0.554
Gnomad4 EAS
AF:
0.767
Gnomad4 SAS
AF:
0.643
Gnomad4 FIN
AF:
0.824
Gnomad4 NFE
AF:
0.694
Gnomad4 OTH
AF:
0.589
Alfa
AF:
0.629
Hom.:
5837
Bravo
AF:
0.599
Asia WGS
AF:
0.661
AC:
2299
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.91
CADD
Benign
0.060
DANN
Benign
0.62

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: rs766083; hg19: chr10-95203404; API