rs141826798

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_030652.4(EGFL8):c.222C>G(p.Tyr74*) variant causes a stop gained, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,614,218 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0033 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 25 hom. )

Consequence

EGFL8
NM_030652.4 stop_gained, splice_region

Scores

Splicing: ADA: 0.5645

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.70

Publications

14 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP6

Variant 6-32166618-C-G is Benign according to our data. Variant chr6-32166618-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2656448.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030652.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFL8	NM_030652.4	MANE Select	c.222C>G	p.Tyr74*	stop_gained splice_region	Exon 3 of 9	NP_085155.1	Q99944
EGFL8	NR_037860.2		n.337C>G		splice_region non_coding_transcript_exon	Exon 3 of 9
PPT2-EGFL8	NR_037861.1		n.1739C>G		splice_region non_coding_transcript_exon	Exon 10 of 16

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
EGFL8	ENST00000333845.11	TSL:1 MANE Select	c.222C>G	p.Tyr74*	stop_gained splice_region	Exon 3 of 9	ENSP00000333380.6	Q99944
EGFL8	ENST00000395512.5	TSL:1	c.222C>G	p.Tyr74*	stop_gained splice_region	Exon 3 of 9	ENSP00000378888.1	Q99944
PPT2-EGFL8	ENST00000422437.5	TSL:5	n.*154C>G		splice_region non_coding_transcript_exon	Exon 11 of 21	ENSP00000457534.1

Frequencies

GnomAD3 genomes

AF:

0.00326

AC:

497

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000989

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00144

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00588

Gnomad OTH

AF:

0.00574

GnomAD2 exomes

AF:

0.00299

AC:

752

AN:

251240

AF XY:

0.00309

show subpopulations

Gnomad AFR exome

AF:

0.00105

Gnomad AMR exome

AF:

0.00153

Gnomad ASJ exome

AF:

0.00268

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00120

Gnomad NFE exome

AF:

0.00513

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.00448

AC:

6546

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00437

AC XY:

3180

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.000806

AC:

AN:

33480

American (AMR)

AF:

0.00179

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00237

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.000684

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00125

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00399

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00540

AC:

6003

AN:

1112006

Other (OTH)

AF:

0.00369

AC:

223

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

428

857

1285

1714

2142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

232

464

696

928

1160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00326

AC:

497

AN:

152340

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

211

AN XY:

74492

show subpopulations

African (AFR)

AF:

0.000986

AC:

AN:

41586

American (AMR)

AF:

0.00144

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00124

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000847

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00588

AC:

400

AN:

68030

Other (OTH)

AF:

0.00568

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00470

Hom.:

Bravo

AF:

0.00314

TwinsUK

AF:

0.00620

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000993

AC:

ESP6500EA

AF:

0.00480

AC:

ExAC

AF:

0.00314

AC:

381

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00534

EpiControl

AF:

0.00640

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.52

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

Eigen

Pathogenic

0.77

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.94

PhyloP100

2.7

Vest4

0.46

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=151/49

disease causing (fs/PTC)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.56

dbscSNV1_RF

Pathogenic

0.73

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over