rs1477800

Variant names:

• chr15-66154577-C-T
• rs1477800
• NM_001385028.1:c.-8-26166G>A

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001385028.1(MEGF11):​c.-8-26166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,142 control chromosomes in the GnomAD database, including 9,513 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 0.32 (9513 hom., cov: 33)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.915
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.526 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.-8-26166G>A		intron	N/A	NP_001371957.1	A0A0A0MS64
	MEGF11	NM_001387150.1		c.-30-26144G>A		intron	N/A	NP_001374079.1	A6BM72-1
	MEGF11	NM_032445.3		c.-8-26166G>A		intron	N/A	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.-8-26166G>A		intron	N/A	ENSP00000378976.2	A0A0A0MS64
	MEGF11	ENST00000422354.6	TSL:1	c.-8-26166G>A		intron	N/A	ENSP00000414475.1	A6BM72-1
	MEGF11	ENST00000288745.7	TSL:1	c.-26-30577G>A		intron	N/A	ENSP00000288745.3	A6BM72-2

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48307 AN: 152024 Hom.: 9509 Cov.: 33

Gnomad AFR AF: 0.0963

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.500

Gnomad ASJ AF: 0.407

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.318 AC: 48313 AN: 152142 Hom.: 9513 Cov.: 33 AF XY: 0.322 AC XY: 23957 AN XY: 74368

African (AFR) AF: 0.0961 AC: 3992 AN: 41544

American (AMR) AF: 0.500 AC: 7643 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 1414 AN: 3472

East Asian (EAS) AF: 0.175 AC: 905 AN: 5168

South Asian (SAS) AF: 0.544 AC: 2619 AN: 4816

European-Finnish (FIN) AF: 0.328 AC: 3463 AN: 10570

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26910 AN: 67986

Other (OTH) AF: 0.360 AC: 758 AN: 2108

Alfa AF: 0.389 Hom.: 17421

Bravo AF: 0.318

Asia WGS AF: 0.349 AC: 1213 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	14
DANN	Benign	0.84
PhyloP100		0.92
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: rs1477800; hg19: chr15-66446915;