rs1891565

Variant names:

• chr10-93338737-C-T
• rs1891565
• NM_013451.4:c.4339-824G>A

Variant summary

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

The NM_013451.4(MYOF):​c.4339-824G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.66 in 151,940 control chromosomes in the GnomAD database, including 34,541 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 0.66 (34541 hom., cov: 30)
• Consequence: MYOF NM_013451.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.949 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOF	NM_013451.4	c.4339-824G>A		intron_variant	Intron 39 of 53	ENST00000359263.9	NP_038479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOF	ENST00000359263.9	c.4339-824G>A		intron_variant	Intron 39 of 53	1	NM_013451.4	ENSP00000352208.4
MYOF	ENST00000358334.9	c.4300-824G>A		intron_variant	Intron 38 of 52	1		ENSP00000351094.5
MYOF	ENST00000463743.5	n.2518-824G>A		intron_variant	Intron 20 of 33	5		ENSP00000432708.1
MYOF	ENST00000475358.1	n.98-824G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.660 AC: 100189 AN: 151822 Hom.: 34520 Cov.: 30

Gnomad AFR AF: 0.448

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.778

Gnomad EAS AF: 0.971

Gnomad SAS AF: 0.839

Gnomad FIN AF: 0.789

Gnomad MID AF: 0.704

Gnomad NFE AF: 0.727

Gnomad OTH AF: 0.673

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

GnomAD4 genome AF: 0.660 AC: 100253 AN: 151940 Hom.: 34541 Cov.: 30 AF XY: 0.665 AC XY: 49393 AN XY: 74260

African (AFR) AF: 0.448 AC: 18531 AN: 41374

American (AMR) AF: 0.658 AC: 10061 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 2701 AN: 3472

East Asian (EAS) AF: 0.971 AC: 5020 AN: 5168

South Asian (SAS) AF: 0.840 AC: 4038 AN: 4808

European-Finnish (FIN) AF: 0.789 AC: 8338 AN: 10564

Middle Eastern (MID) AF: 0.705 AC: 206 AN: 292

European-Non Finnish (NFE) AF: 0.727 AC: 49394 AN: 67960

Other (OTH) AF: 0.675 AC: 1424 AN: 2110

Alfa AF: 0.652 Hom.: 6419

Bravo AF: 0.639

Asia WGS AF: 0.857 AC: 2980 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	0.74
DANN	Benign	0.27
PhyloP100		-0.42
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: rs1891565; hg19: chr10-95098494;