chr15-66159461-G-A

Position:

• chr15-66159461-G-A

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
MEGF11	NM_001385028.1	c.-8-31050C>T		intron_variant		ENST00000395614.6	NP_001371957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEGF11	ENST00000395614.6	c.-8-31050C>T		intron_variant		5	NM_001385028.1	ENSP00000378976.2
MEGF11	ENST00000422354.6	c.-8-31050C>T		intron_variant		1		ENSP00000414475.1
MEGF11	ENST00000288745.7	c.-26-35461C>T		intron_variant		1		ENSP00000288745.3
MEGF11	ENST00000409699.6	c.-30-31028C>T		intron_variant		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

Gnomad4 AFR AF: 0.115

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.214

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.135

Alfa AF: 0.155 Hom.: 3418

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs4776752; hg19: chr15-66451799;