rs3096697

Variant names:

• chr6-32166733-G-A
• rs3096697
• NM_030652.4:c.257G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-32166733-G-A
• chr6-32166733-G-C
• chr6-32166733-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030652.4(EGFL8):​c.257G>A​(p.Arg86Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,592,584 control chromosomes in the GnomAD database, including 35,265 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.18 (2649 hom., cov: 33)
  • Exomes 𝑓: 0.20 (32616 hom.)
• Consequence: EGFL8 NM_030652.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.56
• Publications: 65 publications found

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]

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014428794).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EGFL8	NM_030652.4	c.257G>A	p.Arg86Lys	missense_variant	Exon 4 of 9	ENST00000333845.11	NP_085155.1
EGFL8	NR_037860.2	n.372G>A		non_coding_transcript_exon_variant	Exon 4 of 9
PPT2-EGFL8	NR_037861.1	n.1774G>A		non_coding_transcript_exon_variant	Exon 11 of 16

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EGFL8	ENST00000333845.11	c.257G>A	p.Arg86Lys	missense_variant	Exon 4 of 9	1	NM_030652.4	ENSP00000333380.6
PPT2-EGFL8	ENST00000422437.5	n.*189G>A		non_coding_transcript_exon_variant	Exon 12 of 21	5		ENSP00000457534.1
PPT2-EGFL8	ENST00000422437.5	n.*189G>A		3_prime_UTR_variant	Exon 12 of 21	5		ENSP00000457534.1

Frequencies

GnomAD3 genomes AF: 0.181 AC: 27527 AN: 152094 Hom.: 2652 Cov.: 33

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.0392

Gnomad SAS AF: 0.158

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.168

GnomAD2 exomes AF: 0.156 AC: 36760 AN: 235862 AF XY: 0.158

Gnomad AFR exome AF: 0.196

Gnomad AMR exome AF: 0.0903

Gnomad ASJ exome AF: 0.148

Gnomad EAS exome AF: 0.0362

Gnomad FIN exome AF: 0.137

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.167

GnomAD4 exome AF: 0.204 AC: 293548 AN: 1440372 Hom.: 32616 Cov.: 34 AF XY: 0.201 AC XY: 143375 AN XY: 713810

African (AFR) AF: 0.196 AC: 6484 AN: 33062

American (AMR) AF: 0.0963 AC: 4182 AN: 43436

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 3691 AN: 24488

East Asian (EAS) AF: 0.0226 AC: 893 AN: 39440

South Asian (SAS) AF: 0.137 AC: 11426 AN: 83432

European-Finnish (FIN) AF: 0.140 AC: 7359 AN: 52580

Middle Eastern (MID) AF: 0.0931 AC: 527 AN: 5660

European-Non Finnish (NFE) AF: 0.225 AC: 247541 AN: 1098956

Other (OTH) AF: 0.193 AC: 11445 AN: 59318

GnomAD4 genome AF: 0.181 AC: 27522 AN: 152212 Hom.: 2649 Cov.: 33 AF XY: 0.174 AC XY: 12945 AN XY: 74434

African (AFR) AF: 0.187 AC: 7777 AN: 41534

American (AMR) AF: 0.118 AC: 1803 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3466

East Asian (EAS) AF: 0.0394 AC: 204 AN: 5172

South Asian (SAS) AF: 0.157 AC: 760 AN: 4832

European-Finnish (FIN) AF: 0.141 AC: 1496 AN: 10620

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14375 AN: 67970

Other (OTH) AF: 0.165 AC: 350 AN: 2116

Alfa AF: 0.199 Hom.: 12612

Bravo AF: 0.181

TwinsUK AF: 0.221 AC: 821

ALSPAC AF: 0.229 AC: 881

ESP6500AA AF: 0.187 AC: 825

ESP6500EA AF: 0.216 AC: 1861

ExAC AF: 0.159 AC: 19306

Asia WGS AF: 0.0780 AC: 271 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.0025	T;T;.
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.61
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.46	.;T;T
MetaRNN	Benign	0.0014	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.57	N;N;.
PhyloP100		1.6
PROVEAN	Benign	-0.17	N;N;N
REVEL	Benign	0.021
Sift	Benign	0.75	T;T;T
Sift4G	Benign	0.87	T;T;T
Polyphen		0.0020	B;B;.
Vest4		0.10
MPC		0.45
ClinPred		0.0010	T
GERP RS		3.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.073
gMVP		0.68
Mutation Taster		=94/6	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: rs3096697; hg19: chr6-32134510; COSMIC: COSV61248794; COSMIC: COSV61248794;