15-66155184-T-G

Variant names:

• chr15-66155184-T-G
• rs1477799
• NM_001385028.1:c.-8-26773A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001385028.1(MEGF11):​c.-8-26773A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 152,122 control chromosomes in the GnomAD database, including 21,491 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 0.50 (21491 hom., cov: 33)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0710
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.744 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF11	NM_001385028.1	c.-8-26773A>C		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.-8-26773A>C		intron_variant	Intron 1 of 25	5	NM_001385028.1	ENSP00000378976.2
MEGF11	ENST00000422354.6	c.-8-26773A>C		intron_variant	Intron 1 of 22	1		ENSP00000414475.1
MEGF11	ENST00000288745.7	c.-26-31184A>C		intron_variant	Intron 1 of 20	1		ENSP00000288745.3
MEGF11	ENST00000409699.6	c.-30-26751A>C		intron_variant	Intron 1 of 22	5		ENSP00000386908.2

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75870 AN: 152004 Hom.: 21484 Cov.: 33

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.759

Gnomad AMR AF: 0.659

Gnomad ASJ AF: 0.629

Gnomad EAS AF: 0.764

Gnomad SAS AF: 0.746

Gnomad FIN AF: 0.573

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.576

Gnomad OTH AF: 0.554

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

GnomAD4 genome AF: 0.499 AC: 75883 AN: 152122 Hom.: 21491 Cov.: 33 AF XY: 0.509 AC XY: 37878 AN XY: 74378

African (AFR) AF: 0.213 AC: 8857 AN: 41516

American (AMR) AF: 0.660 AC: 10095 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.629 AC: 2182 AN: 3470

East Asian (EAS) AF: 0.764 AC: 3949 AN: 5170

South Asian (SAS) AF: 0.746 AC: 3600 AN: 4826

European-Finnish (FIN) AF: 0.573 AC: 6055 AN: 10568

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.576 AC: 39108 AN: 67954

Other (OTH) AF: 0.550 AC: 1163 AN: 2114

Alfa AF: 0.558 Hom.: 36447

Bravo AF: 0.492

Asia WGS AF: 0.700 AC: 2434 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.3
DANN	Benign	0.58
PhyloP100		0.071
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: rs1477799; hg19: chr15-66447522;