rs1345663

chr5-127314490-G-A

Variant summary

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

The NM_001256545.2(MEGF10):c.-18-16801G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.615 in 152,046 control chromosomes in the GnomAD database, including 29,272 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 0.61 (29272 hom., cov: 32)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.724

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 -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 = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF10	NM_001256545.2	c.-18-16801G>A		intron_variant		ENST00000503335.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF10	ENST00000503335.7	c.-18-16801G>A		intron_variant		1	NM_001256545.2	P1
MEGF10	ENST00000274473.6	c.-19+14444G>A		intron_variant		1		P1
MEGF10	ENST00000418761.6	c.-19+14444G>A		intron_variant		1
MEGF10	ENST00000508365.5	c.-18-16801G>A		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93436 AN: 151928 Hom.: 29253 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.859

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.576

Gnomad EAS AF: 0.311

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.633

Gnomad MID AF: 0.693

Gnomad NFE AF: 0.679

Gnomad OTH AF: 0.607

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

GnomAD4 genome AF: 0.615 AC: 93486 AN: 152046 Hom.: 29272 Cov.: 32 AF XY: 0.607 AC XY: 45113 AN XY: 74328

Gnomad4 AFR AF: 0.575

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.576

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.526

Gnomad4 FIN AF: 0.633

Gnomad4 NFE AF: 0.679

Gnomad4 OTH AF: 0.610

Alfa AF: 0.658 Hom.: 44702

Bravo AF: 0.604

Asia WGS AF: 0.451 AC: 1569 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	7.1
Dann	Benign	0.66

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: rs1345663; hg19: chr5-126650182; COSMIC: COSV57246728;