rs2096181

chr10-93478104-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.163

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYOF	NM_013451.4	c.88+4003G>A		intron_variant		ENST00000359263.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYOF	ENST00000359263.9	c.88+4003G>A		intron_variant		1	NM_013451.4	P1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 117938 AN: 151834 Hom.: 46262 Cov.: 31

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

Gnomad4 AFR exome AF: 0.763

Gnomad4 AMR exome AF: 0.842

Gnomad4 ASJ exome AF: 0.790

Gnomad4 EAS exome AF: 0.605

Gnomad4 SAS exome AF: 0.875

Gnomad4 FIN exome AF: 0.823

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.824

GnomAD4 genome AF: 0.777 AC: 118030 AN: 151952 Hom.: 46299 Cov.: 31 AF XY: 0.773 AC XY: 57374 AN XY: 74246

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.789

Gnomad4 ASJ AF: 0.779

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.843

Gnomad4 FIN AF: 0.765

Gnomad4 NFE AF: 0.839

Gnomad4 OTH AF: 0.777

Alfa AF: 0.802 Hom.: 7172

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
Dann	Benign	0.16

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

LitVar

Other links and lift over

dbSNP: rs2096181; hg19: chr10-95237861;