Variant rs3130347 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030652.4(EGFL8):c.335-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,592,856 control chromosomes in the GnomAD database, including 35,108 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. There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.18 ( 2513 hom., cov: 32)

Exomes 𝑓: 0.20 ( 32595 hom. )

Consequence

EGFL8
NM_030652.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.94

Variant links:

Genes affected

EGFL8 (HGNC:13944): (EGF like domain multiple 8) Predicted to enable signaling receptor binding activity. Predicted to be involved in anatomical structure development. Predicted to act upstream of or within in utero embryonic development. Predicted to be active in cell surface and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

EGFL8 links:

PPT2-EGFL8 (HGNC:48343): (PPT2-EGFL8 readthrough (NMD candidate)) This locus represents naturally occurring read-through transcription between the neighboring PPT2 (palmitoyl-protein thioesterase 2) and EGFL8 (EGF-like-domain, multiple 8) genes located in the major histocompatibility complex class III region of chromosome 6. The read-through transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is thus unlikely to produce a protein product. [provided by RefSeq, Feb 2011]

PPT2-EGFL8 links:

EGFL8 (HGNC:):

EGFL8 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 0 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
EGFL8	NM_030652.4 linkuse as main transcript	c.335-31T>C	intron_variant	ENST00000333845.11	NP_085155.1	Q99944A0A1U9X7N9
EGFL8	NR_037860.2 linkuse as main transcript	n.450-31T>C	intron_variant
PPT2-EGFL8	NR_037861.1 linkuse as main transcript	n.1852-31T>C	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EGFL8	ENST00000333845.11 linkuse as main transcript	c.335-31T>C		intron_variant		1	NM_030652.4	ENSP00000333380.6		Q99944
PPT2-EGFL8	ENST00000422437.5 linkuse as main transcript	n.*267-31T>C		intron_variant		5		ENSP00000457534.1

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26757

AN:

152030

Hom.:

2516

Cov.:

show subpopulations

Gnomad AFR

AF:

0.170

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.115

Gnomad ASJ

AF:

0.147

Gnomad EAS

AF:

0.0431

Gnomad SAS

AF:

0.159

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.211

Gnomad OTH

AF:

0.165

GnomAD3 exomes

AF:

0.154

AC:

36161

AN:

234878

Hom.:

3236

AF XY:

0.156

AC XY:

19826

AN XY:

127112

show subpopulations

Gnomad AFR exome

AF:

0.179

Gnomad AMR exome

AF:

0.0887

Gnomad ASJ exome

AF:

0.146

Gnomad EAS exome

AF:

0.0385

Gnomad SAS exome

AF:

0.138

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.198

Gnomad OTH exome

AF:

0.164

GnomAD4 exome

AF:

0.204

AC:

293471

AN:

1440708

Hom.:

32595

Cov.:

AF XY:

0.201

AC XY:

143350

AN XY:

714450

show subpopulations

Gnomad4 AFR exome

AF:

0.183

Gnomad4 AMR exome

AF:

0.0939

Gnomad4 ASJ exome

AF:

0.150

Gnomad4 EAS exome

AF:

0.0243

Gnomad4 SAS exome

AF:

0.138

Gnomad4 FIN exome

AF:

0.140

Gnomad4 NFE exome

AF:

0.225

Gnomad4 OTH exome

AF:

0.197

GnomAD4 genome

AF:

0.176

AC:

26751

AN:

152148

Hom.:

2513

Cov.:

AF XY:

0.169

AC XY:

12578

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.170

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.147

Gnomad4 EAS

AF:

0.0432

Gnomad4 SAS

AF:

0.159

Gnomad4 FIN

AF:

0.141

Gnomad4 NFE

AF:

0.211

Gnomad4 OTH

AF:

0.163

Alfa

AF:

0.203

Hom.:

4691

Bravo

AF:

0.175

Asia WGS

AF:

0.0880

AC:

308

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

0.047

DANN

Benign

0.23

BranchPoint Hunter

0.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over