rs246897

Positions:

• chr5-127343710-G-A
• chr5-127343710-G-T

Variant summary

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

The NM_001256545.2(MEGF10):​c.319+3080G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,940 control chromosomes in the GnomAD database, including 13,743 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 (13743 hom., cov: 31)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.569

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=-0.9).
• 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.319+3080G>A		intron_variant		ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.319+3080G>A		intron_variant		1	NM_001256545.2	ENSP00000423354	P1
MEGF10	ENST00000274473.6	c.319+3080G>A		intron_variant		1		ENSP00000274473	P1
MEGF10	ENST00000418761.6	c.319+3080G>A		intron_variant		1		ENSP00000416284
MEGF10	ENST00000508365.5	c.319+3080G>A		intron_variant		1		ENSP00000423195

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61219 AN: 151822 Hom.: 13736 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.408

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.254

Gnomad SAS AF: 0.379

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.403 AC: 61230 AN: 151940 Hom.: 13743 Cov.: 31 AF XY: 0.400 AC XY: 29672 AN XY: 74246

Gnomad4 AFR AF: 0.212

Gnomad4 AMR AF: 0.407

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.254

Gnomad4 SAS AF: 0.379

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.517

Gnomad4 OTH AF: 0.435

Alfa AF: 0.444 Hom.: 1934

Bravo AF: 0.391

Asia WGS AF: 0.329 AC: 1144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.60

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: rs246897; hg19: chr5-126679402; COSMIC: COSV57246877;