rs27652

Variant names:

• chr5-127348191-A-G
• rs27652
• NM_001256545.2:c.319+7561A>G

Variant summary

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

The NM_001256545.2(MEGF10):​c.319+7561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.426 in 151,842 control chromosomes in the GnomAD database, including 14,244 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 0.43 (14244 hom., cov: 32)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• Publications: 3 publications found

Genes affected

MEGF10 (HGNC:29634): (multiple EGF like domains 10) This gene encodes a member of the multiple epidermal growth factor-like domains protein family. The encoded protein plays a role in cell adhesion, motility and proliferation, and is a critical mediator of apoptotic cell phagocytosis as well as amyloid-beta peptide uptake in the brain. Expression of this gene may be associated with schizophrenia, and mutations in this gene are a cause of early-onset myopathy, areflexia, respiratory distress, and dysphagia (EMARDD) as well as congenital myopathy with minicores. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Apr 2012]

MEGF10 Gene-Disease associations (from GenCC):

• MEGF10-related myopathy

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.319+7561A>G		intron_variant	Intron 4 of 24	ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.319+7561A>G		intron_variant	Intron 4 of 24	1	NM_001256545.2	ENSP00000423354.2
MEGF10	ENST00000274473.6	c.319+7561A>G		intron_variant	Intron 5 of 25	1		ENSP00000274473.6
MEGF10	ENST00000418761.6	c.319+7561A>G		intron_variant	Intron 5 of 14	1		ENSP00000416284.2
MEGF10	ENST00000508365.5	c.319+7561A>G		intron_variant	Intron 4 of 13	1		ENSP00000423195.1

Frequencies

GnomAD3 genomes AF: 0.426 AC: 64666 AN: 151724 Hom.: 14228 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.709

Gnomad AMR AF: 0.407

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.462

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.426 AC: 64711 AN: 151842 Hom.: 14244 Cov.: 32 AF XY: 0.423 AC XY: 31345 AN XY: 74186

African (AFR) AF: 0.336 AC: 13934 AN: 41440

American (AMR) AF: 0.407 AC: 6197 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1409 AN: 3466

East Asian (EAS) AF: 0.280 AC: 1453 AN: 5182

South Asian (SAS) AF: 0.380 AC: 1827 AN: 4814

European-Finnish (FIN) AF: 0.445 AC: 4688 AN: 10532

Middle Eastern (MID) AF: 0.466 AC: 136 AN: 292

European-Non Finnish (NFE) AF: 0.494 AC: 33491 AN: 67854

Other (OTH) AF: 0.441 AC: 932 AN: 2114

Alfa AF: 0.472 Hom.: 29728

Bravo AF: 0.419

Asia WGS AF: 0.352 AC: 1225 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.4
DANN	Benign	0.76
PhyloP100		1.8
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: rs27652; hg19: chr5-126683883; COSMIC: COSV57246910;