rs3803414

chr15-65913866-G-A

Variant summary

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

The NM_001385028.1(MEGF11):c.2581C>T(p.Leu861Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0864 in 1,613,902 control chromosomes in the GnomAD database, including 6,754 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 0.062 (351 hom., cov: 32)
  • Exomes 𝑓: 0.089 (6403 hom.)
• Consequence: MEGF11 NM_001385028.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.31

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 (MetaRNN=0.0023320317).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0886 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MEGF11	NM_001385028.1	c.2581C>T	p.Leu861Phe	missense_variant	20/26	ENST00000395614.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MEGF11	ENST00000395614.6	c.2581C>T	p.Leu861Phe	missense_variant	20/26	5	NM_001385028.1	A1

Frequencies

GnomAD3 genomes AF: 0.0623 AC: 9475 AN: 152126 Hom.: 350 Cov.: 32

Gnomad AFR AF: 0.0167

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.0533

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.0521

Gnomad SAS AF: 0.0481

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0904

Gnomad OTH AF: 0.0724

GnomAD3 exomes AF: 0.0697 AC: 17491 AN: 250988 Hom.: 706 AF XY: 0.0720 AC XY: 9767 AN XY: 135638

Gnomad AFR exome AF: 0.0153

Gnomad AMR exome AF: 0.0397

Gnomad ASJ exome AF: 0.110

Gnomad EAS exome AF: 0.0492

Gnomad SAS exome AF: 0.0526

Gnomad FIN exome AF: 0.0603

Gnomad NFE exome AF: 0.0921

Gnomad OTH exome AF: 0.0836

GnomAD4 exome AF: 0.0889 AC: 130013 AN: 1461658 Hom.: 6403 Cov.: 31 AF XY: 0.0882 AC XY: 64158 AN XY: 727114

Gnomad4 AFR exome AF: 0.0154

Gnomad4 AMR exome AF: 0.0409

Gnomad4 ASJ exome AF: 0.109

Gnomad4 EAS exome AF: 0.0623

Gnomad4 SAS exome AF: 0.0535

Gnomad4 FIN exome AF: 0.0581

Gnomad4 NFE exome AF: 0.0979

Gnomad4 OTH exome AF: 0.0840

GnomAD4 genome AF: 0.0622 AC: 9469 AN: 152244 Hom.: 351 Cov.: 32 AF XY: 0.0606 AC XY: 4509 AN XY: 74446

Gnomad4 AFR AF: 0.0167

Gnomad4 AMR AF: 0.0533

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.0516

Gnomad4 SAS AF: 0.0477

Gnomad4 FIN AF: 0.0605

Gnomad4 NFE AF: 0.0905

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0878 Hom.: 1199

Bravo AF: 0.0610

TwinsUK AF: 0.100 AC: 372

ALSPAC AF: 0.101 AC: 391

ESP6500AA AF: 0.0218 AC: 96

ESP6500EA AF: 0.0949 AC: 816

ExAC AF: 0.0691 AC: 8390

Asia WGS AF: 0.0450 AC: 156 AN: 3478

EpiCase AF: 0.0977

EpiControl AF: 0.0971

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.29
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.036	T;.;T;.
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.88	D
MetaRNN	Benign	0.0023	T;T;T;T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.1	M;.;M;.
MutationTaster	Benign	0.040	P;P;P;P;P;P
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N;N;N;.
REVEL	Uncertain	0.29
Sift	Benign	0.22	T;T;T;.
Sift4G	Uncertain	0.033	D;D;D;D
Polyphen		0.91	P;D;P;.
Vest4		0.13
MPC		0.30
ClinPred		0.025	T
GERP RS		3.7
Varity_R		0.073
gMVP		0.47

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: rs3803414; hg19: chr15-66206204; COSMIC: COSV56557050; COSMIC: COSV56557050;