rs1477800

Positions:

• chr15-66154577-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001385028.1(MEGF11):​c.-8-26166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,142 control chromosomes in the GnomAD database, including 9,513 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 0.32 (9513 hom., cov: 33)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF11	NM_001385028.1	c.-8-26166G>A		intron_variant		ENST00000395614.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF11	ENST00000395614.6	c.-8-26166G>A		intron_variant		5	NM_001385028.1	A1
MEGF11	ENST00000288745.7	c.-26-30577G>A		intron_variant		1
MEGF11	ENST00000422354.6	c.-8-26166G>A		intron_variant		1		P2
MEGF11	ENST00000409699.6	c.-30-26144G>A		intron_variant		5		P2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48307 AN: 152024 Hom.: 9509 Cov.: 33

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.318 AC: 48313 AN: 152142 Hom.: 9513 Cov.: 33 AF XY: 0.322 AC XY: 23957 AN XY: 74368

Gnomad4 AFR AF: 0.0961

Gnomad4 AMR AF: 0.500

Gnomad4 ASJ AF: 0.407

Gnomad4 EAS AF: 0.175

Gnomad4 SAS AF: 0.544

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.360

Alfa AF: 0.398 Hom.: 13657

Bravo AF: 0.318

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.84

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: rs1477800; hg19: chr15-66446915;