rs11246286

Positions:

• chr11-715420-G-A
• chr11-715420-G-T

Variant summary

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

The NM_022772.4(EPS8L2):​c.166-4642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 151,862 control chromosomes in the GnomAD database, including 1,407 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 0.13 (1407 hom., cov: 31)
• Consequence: EPS8L2 NM_022772.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180

Genes affected

EPS8L2 (HGNC:21296): (EPS8 signaling adaptor L2) This gene encodes a member of the EPS8 gene family. The encoded protein, like other members of the family, is thought to link growth factor stimulation to actin organization, generating functional redundancy in the pathways that regulate actin cytoskeletal remodeling. [provided by RefSeq, Dec 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.164 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPS8L2	NM_022772.4	c.166-4642G>A		intron_variant		ENST00000318562.13
EPS8L2	XM_017018132.2	c.166-4642G>A		intron_variant
EPS8L2	XM_047427411.1	c.166-4642G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS8L2	ENST00000318562.13	c.166-4642G>A		intron_variant		1	NM_022772.4	P1
	ENST00000527021.2	n.73-6397C>T		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19235 AN: 151744 Hom.: 1408 Cov.: 31

Gnomad AFR AF: 0.0703

Gnomad AMI AF: 0.212

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.0353

Gnomad SAS AF: 0.0535

Gnomad FIN AF: 0.141

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19232 AN: 151862 Hom.: 1407 Cov.: 31 AF XY: 0.124 AC XY: 9196 AN XY: 74210

Gnomad4 AFR AF: 0.0702

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.177

Gnomad4 EAS AF: 0.0356

Gnomad4 SAS AF: 0.0533

Gnomad4 FIN AF: 0.141

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.152

Alfa AF: 0.157 Hom.: 2682

Bravo AF: 0.125

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.24

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: rs11246286; hg19: chr11-715420;