rs17684740

chr5-127384723-T-C

Variant summary

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

The NM_001256545.2(MEGF10):c.413-11809T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,326 control chromosomes in the GnomAD database, including 52 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 0.019 (52 hom., cov: 33)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.08

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 (SAS) allele frequency at 95% confidence interval = 0.0694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF10	NM_001256545.2	c.413-11809T>C		intron_variant		ENST00000503335.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF10	ENST00000503335.7	c.413-11809T>C		intron_variant		1	NM_001256545.2	P1
MEGF10	ENST00000274473.6	c.413-11809T>C		intron_variant		1		P1
MEGF10	ENST00000418761.6	c.413-11809T>C		intron_variant		1
MEGF10	ENST00000508365.5	c.413-11809T>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2921 AN: 152208 Hom.: 51 Cov.: 33

Gnomad AFR AF: 0.0164

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0470

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.0756

Gnomad FIN AF: 0.0215

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0145

Gnomad OTH AF: 0.0187

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

GnomAD4 genome AF: 0.0192 AC: 2920 AN: 152326 Hom.: 52 Cov.: 33 AF XY: 0.0205 AC XY: 1527 AN XY: 74498

Gnomad4 AFR AF: 0.0164

Gnomad4 AMR AF: 0.0114

Gnomad4 ASJ AF: 0.0470

Gnomad4 EAS AF: 0.0469

Gnomad4 SAS AF: 0.0758

Gnomad4 FIN AF: 0.0215

Gnomad4 NFE AF: 0.0145

Gnomad4 OTH AF: 0.0180

Alfa AF: 0.0149 Hom.: 0

Bravo AF: 0.0171

Asia WGS AF: 0.0500 AC: 174 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	0.14
Dann	Benign	0.46

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: rs17684740; hg19: chr5-126720415;