chr6-32168101-G-C

Position:

• chr6-32168101-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030652.4(EGFL8):​c.*145G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0297 in 862,106 control chromosomes in the GnomAD database, including 921 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.

• Frequency:
  • Genomes: 𝑓 0.036 (182 hom., cov: 33)
  • Exomes 𝑓: 0.028 (739 hom.)
• Consequence: EGFL8 NM_030652.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EGFL8	NM_030652.4	c.*145G>C		3_prime_UTR_variant	9/9	ENST00000333845.11
PPT2-EGFL8	NR_037861.1	n.2544G>C		non_coding_transcript_exon_variant	16/16
EGFL8	NR_037860.2	n.1142G>C		non_coding_transcript_exon_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EGFL8	ENST00000333845.11	c.*145G>C		3_prime_UTR_variant	9/9	1	NM_030652.4	P1
EGFL8	ENST00000395512.5	c.*145G>C		3_prime_UTR_variant	9/9	1		P1
EGFL8	ENST00000466239.5	n.2261G>C		non_coding_transcript_exon_variant	6/6	2
EGFL8	ENST00000489721.1	n.275G>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5455 AN: 152212 Hom.: 184 Cov.: 33

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0355

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.0971

Gnomad FIN AF: 0.00301

Gnomad MID AF: 0.0541

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.0469

GnomAD4 exome AF: 0.0284 AC: 20126 AN: 709774 Hom.: 739 Cov.: 9 AF XY: 0.0311 AC XY: 11363 AN XY: 365102

Gnomad4 AFR exome AF: 0.0602

Gnomad4 AMR exome AF: 0.0248

Gnomad4 ASJ exome AF: 0.0146

Gnomad4 EAS exome AF: 0.109

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.00487

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0308

GnomAD4 genome AF: 0.0359 AC: 5465 AN: 152332 Hom.: 182 Cov.: 33 AF XY: 0.0364 AC XY: 2712 AN XY: 74486

Gnomad4 AFR AF: 0.0623

Gnomad4 AMR AF: 0.0354

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.0968

Gnomad4 FIN AF: 0.00301

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.0474

Alfa AF: 0.0191 Hom.: 50

Bravo AF: 0.0377

Asia WGS AF: 0.145 AC: 504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.6
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs205000; hg19: chr6-32135878;