rs1721804

Variant names:

• chr10-93415061-A-G
• rs1721804
• NM_013451.4:c.434-5322T>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.434-5322T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.573 in 151,934 control chromosomes in the GnomAD database, including 30,386 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 0.57 (30386 hom., cov: 31)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.871
• Publications: 2 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013451.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOF	NM_013451.4	MANE Select	c.434-5322T>C		intron	N/A	NP_038479.1	Q9NZM1-1
	MYOF	NM_133337.3		c.434-5322T>C		intron	N/A	NP_579899.1	Q9NZM1-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYOF	ENST00000359263.9	TSL:1 MANE Select	c.434-5322T>C		intron	N/A	ENSP00000352208.4	Q9NZM1-1
	MYOF	ENST00000358334.9	TSL:1	c.434-5322T>C		intron	N/A	ENSP00000351094.5	Q9NZM1-6
	MYOF	ENST00000941957.1		c.434-5322T>C		intron	N/A	ENSP00000612016.1

Frequencies

GnomAD3 genomes AF: 0.573 AC: 87004 AN: 151816 Hom.: 30384 Cov.: 31

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.706

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.705

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.573 AC: 87010 AN: 151934 Hom.: 30386 Cov.: 31 AF XY: 0.577 AC XY: 42832 AN XY: 74238

African (AFR) AF: 0.159 AC: 6586 AN: 41410

American (AMR) AF: 0.677 AC: 10336 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.706 AC: 2448 AN: 3466

East Asian (EAS) AF: 0.342 AC: 1751 AN: 5126

South Asian (SAS) AF: 0.705 AC: 3391 AN: 4810

European-Finnish (FIN) AF: 0.795 AC: 8399 AN: 10566

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.764 AC: 51911 AN: 67980

Other (OTH) AF: 0.624 AC: 1315 AN: 2108

Alfa AF: 0.662 Hom.: 13777

Bravo AF: 0.542

Asia WGS AF: 0.513 AC: 1784 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.0
DANN	Benign	0.27
PhyloP100		-0.87
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: rs1721804; hg19: chr10-95174818;