5-127328347-A-G

Position:

• chr5-127328347-A-G

Variant summary

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

The NM_001256545.2(MEGF10):​c.-18-2944A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 152,056 control chromosomes in the GnomAD database, including 13,667 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 0.40 (13667 hom., cov: 32)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.406

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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.-18-2944A>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.-18-2944A>G		intron_variant		1	NM_001256545.2	ENSP00000423354	P1
MEGF10	ENST00000274473.6	c.-18-2944A>G		intron_variant		1		ENSP00000274473	P1
MEGF10	ENST00000418761.6	c.-18-2944A>G		intron_variant		1		ENSP00000416284
MEGF10	ENST00000508365.5	c.-18-2944A>G		intron_variant		1		ENSP00000423195

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60938 AN: 151938 Hom.: 13661 Cov.: 32

Gnomad AFR AF: 0.203

Gnomad AMI AF: 0.617

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.264

Gnomad SAS AF: 0.384

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.401 AC: 60942 AN: 152056 Hom.: 13667 Cov.: 32 AF XY: 0.397 AC XY: 29510 AN XY: 74324

Gnomad4 AFR AF: 0.202

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.264

Gnomad4 SAS AF: 0.384

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.439

Alfa AF: 0.473 Hom.: 3558

Bravo AF: 0.388

Asia WGS AF: 0.336 AC: 1168 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.1
DANN	Benign	0.69

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: rs36307; hg19: chr5-126664039;