rs3130347

Positions:

• chr6-32166879-T-C

Variant summary

Our verdict is Benign. Variant got -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

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:):

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFL8	NM_030652.4	c.335-31T>C		intron_variant		ENST00000333845.11
PPT2-EGFL8	NR_037861.1	n.1852-31T>C		intron_variant, non_coding_transcript_variant
EGFL8	NR_037860.2	n.450-31T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFL8	ENST00000333845.11	c.335-31T>C		intron_variant		1	NM_030652.4	P1

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

GnomAD3 exomes AF: 0.154 AC: 36161 AN: 234878 Hom.: 3236 AF XY: 0.156 AC XY: 19826 AN XY: 127112

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

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.: 32 AF XY: 0.169 AC XY: 12578 AN XY: 74404

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

Other links and lift over

dbSNP: rs3130347; hg19: chr6-32134656; COSMIC: COSV61248970; COSMIC: COSV61248970;