rs11246286

Variant names:

• chr11-715420-G-A
• rs11246286
• NM_022772.4:c.166-4642G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-715420-G-A
• chr11-715420-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

EPS8L2 Gene-Disease associations (from GenCC):

• hearing loss, autosomal recessive 106

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae)
• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000269915 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
EPS8L2	NM_022772.4	c.166-4642G>A		intron_variant	Intron 4 of 20	ENST00000318562.13	NP_073609.2
EPS8L2	NM_001441192.1	c.166-4642G>A		intron_variant	Intron 5 of 21		NP_001428121.1
EPS8L2	NM_001441193.1	c.166-4642G>A		intron_variant	Intron 5 of 21		NP_001428122.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8L2	ENST00000318562.13	c.166-4642G>A		intron_variant	Intron 4 of 20	1	NM_022772.4	ENSP00000320828.8

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

African (AFR) AF: 0.0702 AC: 2907 AN: 41432

American (AMR) AF: 0.123 AC: 1871 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 615 AN: 3470

East Asian (EAS) AF: 0.0356 AC: 184 AN: 5172

South Asian (SAS) AF: 0.0533 AC: 256 AN: 4804

European-Finnish (FIN) AF: 0.141 AC: 1487 AN: 10522

Middle Eastern (MID) AF: 0.205 AC: 60 AN: 292

European-Non Finnish (NFE) AF: 0.167 AC: 11340 AN: 67928

Other (OTH) AF: 0.152 AC: 319 AN: 2102

Alfa AF: 0.153 Hom.: 3535

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
PhyloP100		0.18
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: rs11246286; hg19: chr11-715420;