rs787625

Variant names:

• chr10-93353734-A-G
• rs787625
• NM_013451.4:c.3481+77T>C

Variant summary

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

The NM_013451.4(MYOF):​c.3481+77T>C variant causes a intron change. The variant allele was found at a frequency of 0.375 in 1,200,024 control chromosomes in the GnomAD database, including 89,565 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 0.33 (8776 hom., cov: 32)
  • Exomes 𝑓: 0.38 (80789 hom.)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.09
• Publications: 4 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=-0.78).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.405 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4	c.3481+77T>C		intron_variant	Intron 32 of 53	ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.3481+77T>C		intron_variant	Intron 32 of 53	1	NM_013451.4	ENSP00000352208.4
MYOF	ENST00000358334.9	c.3442+77T>C		intron_variant	Intron 31 of 52	1		ENSP00000351094.5
MYOF	ENST00000463743.5	n.1603+77T>C		intron_variant	Intron 12 of 33	5		ENSP00000432708.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49408 AN: 151960 Hom.: 8771 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.293

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.409

Gnomad OTH AF: 0.333

GnomAD4 exome AF: 0.382 AC: 400312 AN: 1047946 Hom.: 80789 AF XY: 0.381 AC XY: 200933 AN XY: 527596

African (AFR) AF: 0.195 AC: 4523 AN: 23218

American (AMR) AF: 0.206 AC: 6216 AN: 30154

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 7426 AN: 20304

East Asian (EAS) AF: 0.105 AC: 3853 AN: 36570

South Asian (SAS) AF: 0.300 AC: 19367 AN: 64612

European-Finnish (FIN) AF: 0.440 AC: 21831 AN: 49626

Middle Eastern (MID) AF: 0.322 AC: 1213 AN: 3762

European-Non Finnish (NFE) AF: 0.412 AC: 319177 AN: 774454

Other (OTH) AF: 0.369 AC: 16706 AN: 45246

GnomAD4 genome AF: 0.325 AC: 49435 AN: 152078 Hom.: 8776 Cov.: 32 AF XY: 0.320 AC XY: 23803 AN XY: 74314

African (AFR) AF: 0.211 AC: 8748 AN: 41500

American (AMR) AF: 0.260 AC: 3979 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1272 AN: 3470

East Asian (EAS) AF: 0.0917 AC: 475 AN: 5180

South Asian (SAS) AF: 0.293 AC: 1414 AN: 4822

European-Finnish (FIN) AF: 0.443 AC: 4683 AN: 10560

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.409 AC: 27773 AN: 67948

Other (OTH) AF: 0.335 AC: 708 AN: 2112

Alfa AF: 0.365 Hom.: 2163

Bravo AF: 0.307

Asia WGS AF: 0.208 AC: 722 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	9.8
DANN	Benign	0.79
PhyloP100		4.1
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: rs787625; hg19: chr10-95113491; COSMIC: COSV63703860;