chr5-127331112-A-G

Position:

• chr5-127331112-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001256545.2(MEGF10):​c.-18-179A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 152,284 control chromosomes in the GnomAD database, including 71 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.018 (71 hom., cov: 32)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.214

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-127331112-A-G is Benign according to our data. Variant chr5-127331112-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 672379.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.104 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.-18-179A>G		intron_variant		ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.-18-179A>G		intron_variant		1	NM_001256545.2	ENSP00000423354	P1
MEGF10	ENST00000274473.6	c.-18-179A>G		intron_variant		1		ENSP00000274473	P1
MEGF10	ENST00000418761.6	c.-18-179A>G		intron_variant		1		ENSP00000416284
MEGF10	ENST00000508365.5	c.-18-179A>G		intron_variant		1		ENSP00000423195

Frequencies

GnomAD3 genomes AF: 0.0181 AC: 2755 AN: 152166 Hom.: 69 Cov.: 32

Gnomad AFR AF: 0.00560

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.0521

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.0909

Gnomad FIN AF: 0.0194

Gnomad MID AF: 0.0924

Gnomad NFE AF: 0.0125

Gnomad OTH AF: 0.0192

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

GnomAD4 genome AF: 0.0181 AC: 2751 AN: 152284 Hom.: 71 Cov.: 32 AF XY: 0.0199 AC XY: 1484 AN XY: 74462

Gnomad4 AFR AF: 0.00556

Gnomad4 AMR AF: 0.0119

Gnomad4 ASJ AF: 0.0521

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0908

Gnomad4 FIN AF: 0.0194

Gnomad4 NFE AF: 0.0125

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.0107 Hom.: 3

Bravo AF: 0.0156

Asia WGS AF: 0.0840 AC: 291 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	4.7
DANN	Benign	0.70

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: rs80220399; hg19: chr5-126666804;