chr10-93404449-T-C

Variant names:

• chr10-93404449-T-C
• rs701864
• NM_013451.4:c.730-230A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_013451.4(MYOF):​c.730-230A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.538 in 152,028 control chromosomes in the GnomAD database, including 26,707 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 0.54 (26707 hom., cov: 30)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 3 publications found

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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4	c.730-230A>G		intron_variant	Intron 7 of 53	ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.730-230A>G		intron_variant	Intron 7 of 53	1	NM_013451.4	ENSP00000352208.4
MYOF	ENST00000358334.9	c.730-230A>G		intron_variant	Intron 7 of 52	1		ENSP00000351094.5
MYOF	ENST00000371489.5	c.730-230A>G		intron_variant	Intron 7 of 14	2		ENSP00000360544.1

Frequencies

GnomAD3 genomes AF: 0.538 AC: 81793 AN: 151912 Hom.: 26698 Cov.: 30

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.665

Gnomad ASJ AF: 0.680

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.712

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.696

Gnomad NFE AF: 0.700

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.538 AC: 81813 AN: 152028 Hom.: 26707 Cov.: 30 AF XY: 0.545 AC XY: 40469 AN XY: 74274

African (AFR) AF: 0.151 AC: 6261 AN: 41484

American (AMR) AF: 0.665 AC: 10159 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.680 AC: 2360 AN: 3472

East Asian (EAS) AF: 0.363 AC: 1874 AN: 5164

South Asian (SAS) AF: 0.712 AC: 3426 AN: 4810

European-Finnish (FIN) AF: 0.754 AC: 7949 AN: 10540

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.700 AC: 47578 AN: 67964

Other (OTH) AF: 0.611 AC: 1287 AN: 2108

Alfa AF: 0.640 Hom.: 100611

Bravo AF: 0.513

Asia WGS AF: 0.535 AC: 1860 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.52
DANN	Benign	0.52
PhyloP100		-1.1
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: rs701864; hg19: chr10-95164206;