rs333603

Variant names:

• chr15-66047062-G-A
• rs333603
• NM_001385028.1:c.394+47340C>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.394+47340C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 152,108 control chromosomes in the GnomAD database, including 33,174 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 0.64 (33174 hom., cov: 32)
• Consequence: MEGF11 NM_001385028.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEGF11	NM_001385028.1	c.394+47340C>T		intron_variant	Intron 5 of 25	ENST00000395614.6	NP_001371957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEGF11	ENST00000395614.6	c.394+47340C>T		intron_variant	Intron 5 of 25	5	NM_001385028.1	ENSP00000378976.2
MEGF11	ENST00000422354.6	c.394+47340C>T		intron_variant	Intron 5 of 22	1		ENSP00000414475.1
MEGF11	ENST00000288745.7	c.169+47340C>T		intron_variant	Intron 3 of 20	1		ENSP00000288745.3
MEGF11	ENST00000409699.6	c.394+47340C>T		intron_variant	Intron 5 of 22	5		ENSP00000386908.2

Frequencies

GnomAD3 genomes AF: 0.637 AC: 96798 AN: 151990 Hom.: 33173 Cov.: 32

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.831

Gnomad AMR AF: 0.772

Gnomad ASJ AF: 0.724

Gnomad EAS AF: 0.362

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.663

Gnomad MID AF: 0.747

Gnomad NFE AF: 0.763

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.637 AC: 96820 AN: 152108 Hom.: 33174 Cov.: 32 AF XY: 0.632 AC XY: 46958 AN XY: 74350

African (AFR) AF: 0.395 AC: 16393 AN: 41472

American (AMR) AF: 0.772 AC: 11815 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.724 AC: 2511 AN: 3470

East Asian (EAS) AF: 0.362 AC: 1870 AN: 5166

South Asian (SAS) AF: 0.603 AC: 2911 AN: 4824

European-Finnish (FIN) AF: 0.663 AC: 7009 AN: 10572

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.763 AC: 51901 AN: 67990

Other (OTH) AF: 0.680 AC: 1433 AN: 2108

Alfa AF: 0.715 Hom.: 29848

Bravo AF: 0.633

Asia WGS AF: 0.464 AC: 1618 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.5
DANN	Benign	0.34
PhyloP100		-0.032
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: rs333603; hg19: chr15-66339400;