rs11071868

Variant names:

• chr15-66183864-G-A
• rs11071868
• NM_001385028.1:c.-8-55453C>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.-8-55453C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 152,036 control chromosomes in the GnomAD database, including 4,161 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 0.22 (4161 hom., cov: 31)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 3 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 (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF11	NM_001385028.1	c.-8-55453C>T		intron_variant	Intron 1 of 25	ENST00000395614.6	NP_001371957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF11	ENST00000395614.6	c.-8-55453C>T		intron_variant	Intron 1 of 25	5	NM_001385028.1	ENSP00000378976.2
MEGF11	ENST00000422354.6	c.-8-55453C>T		intron_variant	Intron 1 of 22	1		ENSP00000414475.1
MEGF11	ENST00000288745.7	c.-26-59864C>T		intron_variant	Intron 1 of 20	1		ENSP00000288745.3
MEGF11	ENST00000409699.6	c.-30-55431C>T		intron_variant	Intron 1 of 22	5		ENSP00000386908.2

Frequencies

GnomAD3 genomes AF: 0.221 AC: 33643 AN: 151918 Hom.: 4161 Cov.: 31

Gnomad AFR AF: 0.179

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.183

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.216

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

GnomAD4 genome AF: 0.221 AC: 33659 AN: 152036 Hom.: 4161 Cov.: 31 AF XY: 0.225 AC XY: 16701 AN XY: 74314

African (AFR) AF: 0.179 AC: 7418 AN: 41472

American (AMR) AF: 0.284 AC: 4337 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.183 AC: 636 AN: 3470

East Asian (EAS) AF: 0.516 AC: 2662 AN: 5160

South Asian (SAS) AF: 0.203 AC: 979 AN: 4816

European-Finnish (FIN) AF: 0.251 AC: 2649 AN: 10566

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14361 AN: 67948

Other (OTH) AF: 0.215 AC: 454 AN: 2108

Alfa AF: 0.210 Hom.: 5124

Bravo AF: 0.222

Asia WGS AF: 0.324 AC: 1123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		0.060
Mutation Taster		=100/0	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: rs11071868; hg19: chr15-66476202;