dbSNP rs143954261: MEGF10:c.413-2774G>C (chr5-127393758-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The NM_001256545.2(MEGF10):c.413-2774G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0255 in 151,886 control chromosomes in the GnomAD database, including 74 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 0.026 ( 74 hom., cov: 32)

Consequence

MEGF10
NM_001256545.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.675

Publications

6 publications found

Variant links:

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]

MEGF10 Gene-Disease associations (from GenCC):

MEGF10-related myopathy
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), ClinGen

MEGF10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0255 (3876/151886) while in subpopulation NFE AF = 0.0407 (2768/67944). AF 95% confidence interval is 0.0395. There are 74 homozygotes in GnomAd4. There are 1757 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF10	NM_001256545.2 link	c.413-2774G>C		intron_variant	Intron 5 of 24	ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
MEGF10	ENST00000503335.7 link	c.413-2774G>C	intron_variant	Intron 5 of 24	1	NM_001256545.2	ENSP00000423354.2
MEGF10	ENST00000274473.6 link	c.413-2774G>C	intron_variant	Intron 6 of 25	1		ENSP00000274473.6
MEGF10	ENST00000418761.6 link	c.413-2774G>C	intron_variant	Intron 6 of 14	1		ENSP00000416284.2
MEGF10	ENST00000508365.5 link	c.413-2774G>C	intron_variant	Intron 5 of 13	1		ENSP00000423195.1

Frequencies

GnomAD3 genomes

AF:

0.0255

AC:

3875

AN:

151780

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00784

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.0285

Gnomad ASJ

AF:

0.0393

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00312

Gnomad FIN

AF:

0.0111

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0407

Gnomad OTH

AF:

0.0365

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

GnomAD4 genome

AF:

0.0255

AC:

3876

AN:

151886

Hom.:

Cov.:

AF XY:

0.0237

AC XY:

1757

AN XY:

74218

show subpopulations

African (AFR)

AF:

0.00782

AC:

324

AN:

41442

American (AMR)

AF:

0.0284

AC:

434

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.0393

AC:

136

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00313

AC:

AN:

4800

European-Finnish (FIN)

AF:

0.0111

AC:

117

AN:

10496

Middle Eastern (MID)

AF:

0.00685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0407

AC:

2768

AN:

67944

Other (OTH)

AF:

0.0362

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

195

390

584

779

974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0305

Hom.:

Bravo

AF:

0.0261

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

6.4

(source)

DANN

Benign

0.54

PhyloP100

0.68

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over