15-66187878-G-T

Variant names:

• chr15-66187878-G-T
• rs899079
• NM_001385028.1:c.-8-59467C>A

Variant summary

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

The NM_001385028.1(MEGF11):​c.-8-59467C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,140 control chromosomes in the GnomAD database, including 28,309 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 0.60 (28309 hom., cov: 32)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06
• 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=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.762 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF11	NM_001385028.1	c.-8-59467C>A		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.-8-59467C>A		intron_variant	Intron 1 of 25	5	NM_001385028.1	ENSP00000378976.2
MEGF11	ENST00000422354.6	c.-8-59467C>A		intron_variant	Intron 1 of 22	1		ENSP00000414475.1
MEGF11	ENST00000288745.7	c.-26-63878C>A		intron_variant	Intron 1 of 20	1		ENSP00000288745.3
MEGF11	ENST00000409699.6	c.-30-59445C>A		intron_variant	Intron 1 of 22	5		ENSP00000386908.2

Frequencies

GnomAD3 genomes AF: 0.596 AC: 90631 AN: 152022 Hom.: 28287 Cov.: 32

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.655

Gnomad ASJ AF: 0.620

Gnomad EAS AF: 0.693

Gnomad SAS AF: 0.551

Gnomad FIN AF: 0.476

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.491

Gnomad OTH AF: 0.600

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

GnomAD4 genome AF: 0.596 AC: 90692 AN: 152140 Hom.: 28309 Cov.: 32 AF XY: 0.596 AC XY: 44291 AN XY: 74364

African (AFR) AF: 0.769 AC: 31932 AN: 41506

American (AMR) AF: 0.656 AC: 10030 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.620 AC: 2151 AN: 3470

East Asian (EAS) AF: 0.693 AC: 3589 AN: 5182

South Asian (SAS) AF: 0.550 AC: 2655 AN: 4826

European-Finnish (FIN) AF: 0.476 AC: 5031 AN: 10568

Middle Eastern (MID) AF: 0.585 AC: 172 AN: 294

European-Non Finnish (NFE) AF: 0.491 AC: 33381 AN: 67972

Other (OTH) AF: 0.596 AC: 1258 AN: 2112

Alfa AF: 0.524 Hom.: 14265

Bravo AF: 0.620

Asia WGS AF: 0.614 AC: 2135 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.28
DANN	Benign	0.66
PhyloP100		-1.1
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: rs899079; hg19: chr15-66480216;