15-66155184-T-G

Variant summary

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

The NM_001385028.1(MEGF11):c.-8-26773A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,122 control chromosomes in the GnomAD database, including 21,491 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 0.50 (21491 hom., cov: 33)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710

Genes affected

MEGF11 (HGNC:29635): (multiple EGF like domains 11) Predicted to be involved in homotypic cell-cell adhesion and retina layer formation. Predicted to be located in basolateral plasma membrane. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

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 (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF11	NM_001385028.1	c.-8-26773A>C		intron_variant		ENST00000395614.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF11	ENST00000395614.6	c.-8-26773A>C		intron_variant		5	NM_001385028.1	A1
MEGF11	ENST00000288745.7	c.-26-31184A>C		intron_variant		1
MEGF11	ENST00000422354.6	c.-8-26773A>C		intron_variant		1		P2
MEGF11	ENST00000409699.6	c.-30-26751A>C		intron_variant		5		P2

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75870 AN: 152004 Hom.: 21484 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.499 AC: 75883 AN: 152122 Hom.: 21491 Cov.: 33 AF XY: 0.509 AC XY: 37878 AN XY: 74378

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.660

Gnomad4 ASJ AF: 0.629

Gnomad4 EAS AF: 0.764

Gnomad4 SAS AF: 0.746

Gnomad4 FIN AF: 0.573

Gnomad4 NFE AF: 0.576

Gnomad4 OTH AF: 0.550

Alfa AF: 0.568 Hom.: 24764

Bravo AF: 0.492

Asia WGS AF: 0.700 AC: 2434 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.3
Dann	Benign	0.58

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: rs1477799; hg19: chr15-66447522;