rs4776752

Variant names:

• chr15-66159461-G-A
• rs4776752
• NM_001385028.1:c.-8-31050C>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.-8-31050C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.153 in 152,170 control chromosomes in the GnomAD database, including 2,035 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 0.15 (2035 hom., cov: 32)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 2 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 = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF11	NM_001385028.1	c.-8-31050C>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.-8-31050C>T		intron_variant	Intron 1 of 25	5	NM_001385028.1	ENSP00000378976.2
MEGF11	ENST00000422354.6	c.-8-31050C>T		intron_variant	Intron 1 of 22	1		ENSP00000414475.1
MEGF11	ENST00000288745.7	c.-26-35461C>T		intron_variant	Intron 1 of 20	1		ENSP00000288745.3
MEGF11	ENST00000409699.6	c.-30-31028C>T		intron_variant	Intron 1 of 22	5		ENSP00000386908.2

Frequencies

GnomAD3 genomes AF: 0.153 AC: 23250 AN: 152052 Hom.: 2037 Cov.: 32

Gnomad AFR AF: 0.115

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.387

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.214

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.136

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

GnomAD4 genome AF: 0.153 AC: 23264 AN: 152170 Hom.: 2035 Cov.: 32 AF XY: 0.156 AC XY: 11628 AN XY: 74380

African (AFR) AF: 0.115 AC: 4758 AN: 41518

American (AMR) AF: 0.113 AC: 1723 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.129 AC: 447 AN: 3472

East Asian (EAS) AF: 0.388 AC: 2006 AN: 5172

South Asian (SAS) AF: 0.183 AC: 881 AN: 4818

European-Finnish (FIN) AF: 0.214 AC: 2265 AN: 10572

Middle Eastern (MID) AF: 0.160 AC: 47 AN: 294

European-Non Finnish (NFE) AF: 0.158 AC: 10764 AN: 67998

Other (OTH) AF: 0.135 AC: 285 AN: 2114

Alfa AF: 0.153 Hom.: 5871

Bravo AF: 0.145

Asia WGS AF: 0.237 AC: 827 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	0.21
DANN	Benign	0.40
PhyloP100		-1.3
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: rs4776752; hg19: chr15-66451799;