rs3803414

Variant names:

• chr15-65913866-G-A
• rs3803414
• NM_001385028.1:c.2581C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 23 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001385028.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF11	NM_001385028.1	MANE Select	c.2581C>T	p.Leu861Phe	missense	Exon 20 of 26	NP_001371957.1	A0A0A0MS64
	MEGF11	NM_001387150.1		c.2581C>T	p.Leu861Phe	missense	Exon 20 of 23	NP_001374079.1	A6BM72-1
	MEGF11	NM_032445.3		c.2581C>T	p.Leu861Phe	missense	Exon 20 of 23	NP_115821.2	A6BM72-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MEGF11	ENST00000395614.6	TSL:5 MANE Select	c.2581C>T	p.Leu861Phe	missense	Exon 20 of 26	ENSP00000378976.2	A0A0A0MS64
	MEGF11	ENST00000422354.6	TSL:1	c.2581C>T	p.Leu861Phe	missense	Exon 20 of 23	ENSP00000414475.1	A6BM72-1
	MEGF11	ENST00000288745.7	TSL:1	c.2356C>T	p.Leu786Phe	missense	Exon 18 of 21	ENSP00000288745.3	A6BM72-2

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

GnomAD2 exomes AF: 0.0697 AC: 17491 AN: 250988 AF XY: 0.0720

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 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

African (AFR) AF: 0.0154 AC: 514 AN: 33480

American (AMR) AF: 0.0409 AC: 1827 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.109 AC: 2843 AN: 26134

East Asian (EAS) AF: 0.0623 AC: 2473 AN: 39700

South Asian (SAS) AF: 0.0535 AC: 4617 AN: 86258

European-Finnish (FIN) AF: 0.0581 AC: 3103 AN: 53394

Middle Eastern (MID) AF: 0.123 AC: 712 AN: 5768

European-Non Finnish (NFE) AF: 0.0979 AC: 108850 AN: 1111834

Other (OTH) AF: 0.0840 AC: 5074 AN: 60374

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

African (AFR) AF: 0.0167 AC: 693 AN: 41546

American (AMR) AF: 0.0533 AC: 815 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3472

East Asian (EAS) AF: 0.0516 AC: 267 AN: 5174

South Asian (SAS) AF: 0.0477 AC: 230 AN: 4820

European-Finnish (FIN) AF: 0.0605 AC: 642 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0905 AC: 6154 AN: 68008

Other (OTH) AF: 0.0716 AC: 151 AN: 2108

Alfa AF: 0.0851 Hom.: 2194

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 v4.9

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
Eigen	Uncertain	0.33
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.0023	T
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.3
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.3	N
REVEL	Uncertain	0.29
Sift	Benign	0.22	T
Sift4G	Uncertain	0.033	D
Polyphen		0.91	P
Vest4		0.13
MPC		0.30
ClinPred		0.025	T
GERP RS		3.7
Varity_R		0.073
gMVP		0.47
Mutation Taster		=86/14	polymorphism (auto)

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

Other links and lift over

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