rs1477798

chr15-66159908-T-C

Variant summary

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

The NM_001385028.1(MEGF11):c.-8-31497A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,898 control chromosomes in the GnomAD database, including 41,896 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 0.74 (41896 hom., cov: 30)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.835 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF11	NM_001385028.1	c.-8-31497A>G		intron_variant		ENST00000395614.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF11	ENST00000395614.6	c.-8-31497A>G		intron_variant		5	NM_001385028.1	A1
MEGF11	ENST00000288745.7	c.-26-35908A>G		intron_variant		1
MEGF11	ENST00000422354.6	c.-8-31497A>G		intron_variant		1		P2
MEGF11	ENST00000409699.6	c.-30-31475A>G		intron_variant		5		P2

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112647 AN: 151780 Hom.: 41881 Cov.: 30

Gnomad AFR AF: 0.722

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.829

Gnomad ASJ AF: 0.732

Gnomad EAS AF: 0.856

Gnomad SAS AF: 0.794

Gnomad FIN AF: 0.752

Gnomad MID AF: 0.794

Gnomad NFE AF: 0.721

Gnomad OTH AF: 0.767

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

GnomAD4 genome AF: 0.742 AC: 112709 AN: 151898 Hom.: 41896 Cov.: 30 AF XY: 0.747 AC XY: 55463 AN XY: 74250

Gnomad4 AFR AF: 0.722

Gnomad4 AMR AF: 0.829

Gnomad4 ASJ AF: 0.732

Gnomad4 EAS AF: 0.856

Gnomad4 SAS AF: 0.793

Gnomad4 FIN AF: 0.752

Gnomad4 NFE AF: 0.721

Gnomad4 OTH AF: 0.761

Alfa AF: 0.731 Hom.: 24723

Bravo AF: 0.746

Asia WGS AF: 0.818 AC: 2849 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	3.6
Dann	Benign	0.33

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: rs1477798; hg19: chr15-66452246;