dbSNP rs2096181: MYOF:c.88+4003G>A (chr10-93478104-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_013451.4(MYOF):c.88+4003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 229,168 control chromosomes in the GnomAD database, including 74,098 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 0.78 ( 46299 hom., cov: 31)

Exomes 𝑓: 0.85 ( 27799 hom. )

Consequence

MYOF
NM_013451.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.163

Publications

3 publications found

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]

MYOF Gene-Disease associations (from GenCC):

angioedema, hereditary, 7
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

MYOF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.99).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.834 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4 link	c.88+4003G>A		intron_variant	Intron 1 of 53	ENST00000359263.9	NP_038479.1	Q9NZM1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9 link	c.88+4003G>A		intron_variant	Intron 1 of 53	1	NM_013451.4	ENSP00000352208.4		Q9NZM1-1

Frequencies

GnomAD3 genomes

AF:

0.777

AC:

117938

AN:

151834

Hom.:

46262

Cov.:

show subpopulations

Gnomad AFR

AF:

0.700

Gnomad AMI

AF:

0.825

Gnomad AMR

AF:

0.788

Gnomad ASJ

AF:

0.779

Gnomad EAS

AF:

0.480

Gnomad SAS

AF:

0.844

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.839

Gnomad OTH

AF:

0.777

GnomAD4 exome

AF:

0.846

AC:

65295

AN:

77216

Hom.:

27799

AF XY:

0.842

AC XY:

42191

AN XY:

50102

show subpopulations

African (AFR)

AF:

0.763

AC:

746

AN:

978

American (AMR)

AF:

0.842

AC:

2590

AN:

3076

Ashkenazi Jewish (ASJ)

AF:

0.790

AC:

1761

AN:

2230

East Asian (EAS)

AF:

0.605

AC:

1402

AN:

2318

South Asian (SAS)

AF:

0.875

AC:

10510

AN:

12012

European-Finnish (FIN)

AF:

0.823

AC:

2275

AN:

2764

Middle Eastern (MID)

AF:

0.748

AC:

184

AN:

246

European-Non Finnish (NFE)

AF:

0.857

AC:

42932

AN:

50080

Other (OTH)

AF:

0.824

AC:

2895

AN:

3512

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.541

Heterozygous variant carriers

415

830

1244

1659

2074

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.777

AC:

118030

AN:

151952

Hom.:

46299

Cov.:

AF XY:

0.773

AC XY:

57374

AN XY:

74246

show subpopulations

African (AFR)

AF:

0.700

AC:

29009

AN:

41426

American (AMR)

AF:

0.789

AC:

12042

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.779

AC:

2704

AN:

3470

East Asian (EAS)

AF:

0.480

AC:

2475

AN:

5158

South Asian (SAS)

AF:

0.843

AC:

4061

AN:

4816

European-Finnish (FIN)

AF:

0.765

AC:

8023

AN:

10488

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.839

AC:

57090

AN:

68006

Other (OTH)

AF:

0.777

AC:

1644

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1301

2602

3902

5203

6504

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

864

1728

2592

3456

4320

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.799

Hom.:

7375

Bravo

AF:

0.769

Asia WGS

AF:

0.675

AC:

2342

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.99

CADD

Benign

2.1

(source)

DANN

Benign

0.16

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over