rs3130347

Variant names:

• chr6-32166879-T-C
• rs3130347
• NM_030652.4:c.335-31T>C

Your query was ambiguous. Multiple possible variants found:

• chr6-32166879-T-C
• chr6-32166879-T-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.94
• Publications: 28 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: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 0 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. 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.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL8	NM_030652.4	MANE Select	c.335-31T>C		intron	N/A	NP_085155.1
	EGFL8	NR_037860.2		n.450-31T>C		intron	N/A
	PPT2-EGFL8	NR_037861.1		n.1852-31T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EGFL8	ENST00000333845.11	TSL:1 MANE Select	c.335-31T>C		intron	N/A	ENSP00000333380.6
	EGFL8	ENST00000395512.5	TSL:1	c.335-31T>C		intron	N/A	ENSP00000378888.1
	PPT2-EGFL8	ENST00000422437.5	TSL:5	n.*267-31T>C		intron	N/A	ENSP00000457534.1

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26757 AN: 152030 Hom.: 2516 Cov.: 32

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

GnomAD2 exomes AF: 0.154 AC: 36161 AN: 234878 AF XY: 0.156

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 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.: 34 AF XY: 0.201 AC XY: 143350 AN XY: 714450

African (AFR) AF: 0.183 AC: 6005 AN: 32896

American (AMR) AF: 0.0939 AC: 3982 AN: 42414

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 3702 AN: 24654

East Asian (EAS) AF: 0.0243 AC: 958 AN: 39476

South Asian (SAS) AF: 0.138 AC: 11528 AN: 83806

European-Finnish (FIN) AF: 0.140 AC: 7369 AN: 52706

Middle Eastern (MID) AF: 0.0922 AC: 522 AN: 5660

European-Non Finnish (NFE) AF: 0.225 AC: 247708 AN: 1099812

Other (OTH) AF: 0.197 AC: 11697 AN: 59284

GnomAD4 genome AF: 0.176 AC: 26751 AN: 152148 Hom.: 2513 Cov.: 32 AF XY: 0.169 AC XY: 12578 AN XY: 74404

African (AFR) AF: 0.170 AC: 7055 AN: 41518

American (AMR) AF: 0.114 AC: 1747 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 509 AN: 3464

East Asian (EAS) AF: 0.0432 AC: 223 AN: 5166

South Asian (SAS) AF: 0.159 AC: 765 AN: 4826

European-Finnish (FIN) AF: 0.141 AC: 1488 AN: 10588

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

European-Non Finnish (NFE) AF: 0.211 AC: 14372 AN: 67972

Other (OTH) AF: 0.163 AC: 344 AN: 2112

Alfa AF: 0.201 Hom.: 12559

Bravo AF: 0.175

Asia WGS AF: 0.0880 AC: 308 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.047
DANN	Benign	0.23
PhyloP100		-1.9
BranchPoint Hunter		0.0
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: rs3130347; hg19: chr6-32134656; COSMIC: COSV61248970; COSMIC: COSV61248970;