rs143954261

Positions:

• chr5-127393758-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.675

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=-0.82).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 74 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MEGF10	NM_001256545.2	c.413-2774G>C		intron_variant		ENST00000503335.7	NP_001243474.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF10	ENST00000503335.7	c.413-2774G>C		intron_variant		1	NM_001256545.2	ENSP00000423354	P1
MEGF10	ENST00000274473.6	c.413-2774G>C		intron_variant		1		ENSP00000274473	P1
MEGF10	ENST00000418761.6	c.413-2774G>C		intron_variant		1		ENSP00000416284
MEGF10	ENST00000508365.5	c.413-2774G>C		intron_variant		1		ENSP00000423195

Frequencies

GnomAD3 genomes AF: 0.0255 AC: 3875 AN: 151780 Hom.: 74 Cov.: 32

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.: 74 Cov.: 32 AF XY: 0.0237 AC XY: 1757 AN XY: 74218

Gnomad4 AFR AF: 0.00782

Gnomad4 AMR AF: 0.0284

Gnomad4 ASJ AF: 0.0393

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00313

Gnomad4 FIN AF: 0.0111

Gnomad4 NFE AF: 0.0407

Gnomad4 OTH AF: 0.0362

Alfa AF: 0.0305 Hom.: 14

Bravo AF: 0.0261

Asia WGS AF: 0.00318 AC: 11 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
DANN	Benign	0.54

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: rs143954261; hg19: chr5-126729450;