5-127299975-G-C

Position:

• chr5-127299975-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001256545.2(MEGF10):​c.-19+8919G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,934 control chromosomes in the GnomAD database, including 22,334 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (22334 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MEGF10 NM_001256545.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.886

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 5-127299975-G-C is Benign according to our data. Variant chr5-127299975-G-C is described in ClinVar as [Benign]. Clinvar id is 1295222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF10	NM_001256545.2	c.-19+8919G>C		intron_variant		ENST00000503335.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF10	ENST00000503335.7	c.-19+8919G>C		intron_variant		1	NM_001256545.2	P1
MEGF10	ENST00000274473.6	c.-69-21G>C		intron_variant		1		P1
MEGF10	ENST00000418761.6	c.-69-21G>C		intron_variant		1
MEGF10	ENST00000508365.5	c.-19+8919G>C		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80939 AN: 151812 Hom.: 22317 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.277

Gnomad SAS AF: 0.415

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.627

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.550

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.533 AC: 80988 AN: 151930 Hom.: 22334 Cov.: 31 AF XY: 0.524 AC XY: 38877 AN XY: 74240

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.508

Gnomad4 ASJ AF: 0.548

Gnomad4 EAS AF: 0.276

Gnomad4 SAS AF: 0.415

Gnomad4 FIN AF: 0.516

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.555

Alfa AF: 0.366 Hom.: 774

Bravo AF: 0.527

Asia WGS AF: 0.397 AC: 1383 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		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: rs1345662; hg19: chr5-126635667; COSMIC: COSV57246575;