dbSNP rs4343077: EPS8:c.-22+8904C>T (chr12-15780257-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004447.6(EPS8):c.-22+8904C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 151,908 control chromosomes in the GnomAD database, including 38,810 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 0.67 ( 38807 hom., cov: 30)

Exomes 𝑓: 0.75 ( 3 hom. )

Consequence

EPS8
NM_004447.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.45

Publications

5 publications found

Variant links:

Genes affected

EPS8 (HGNC:3420): (EGFR pathway substrate 8, signaling adaptor) This gene encodes a member of the EPS8 family. This protein contains one PH domain and one SH3 domain. It functions as part of the EGFR pathway, though its exact role has not been determined. Highly similar proteins in other organisms are involved in the transduction of signals from Ras to Rac and growth factor-mediated actin remodeling. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]

EPS8 Gene-Disease associations (from GenCC):

autosomal recessive nonsyndromic hearing loss 102
Inheritance: AR Classification: STRONG, MODERATE Submitted by: ClinGen, PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae)
hearing loss, autosomal recessive
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

EPS8 links:

ENSG00000255565 (HGNC:):

ENSG00000255565 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.849 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8	NM_004447.6 link	c.-22+8904C>T		intron_variant	Intron 1 of 20	ENST00000281172.10	NP_004438.3	Q12929-1B4E3T6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10 link	c.-22+8904C>T		intron_variant	Intron 1 of 20	1	NM_004447.6	ENSP00000281172.5		Q12929-1

Frequencies

GnomAD3 genomes

AF:

0.674

AC:

102232

AN:

151782

Hom.:

38818

Cov.:

show subpopulations

Gnomad AFR

AF:

0.298

Gnomad AMI

AF:

0.774

Gnomad AMR

AF:

0.682

Gnomad ASJ

AF:

0.764

Gnomad EAS

AF:

0.861

Gnomad SAS

AF:

0.871

Gnomad FIN

AF:

0.829

Gnomad MID

AF:

0.759

Gnomad NFE

AF:

0.840

Gnomad OTH

AF:

0.686

GnomAD4 exome

AF:

0.750

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

1.00

AC:

AN:

Other (OTH)

AC:

AN:

GnomAD4 genome

AF:

0.673

AC:

102230

AN:

151900

Hom.:

38807

Cov.:

AF XY:

0.677

AC XY:

50291

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.298

AC:

12323

AN:

41362

American (AMR)

AF:

0.681

AC:

10382

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.764

AC:

2651

AN:

3468

East Asian (EAS)

AF:

0.861

AC:

4448

AN:

5166

South Asian (SAS)

AF:

0.871

AC:

4195

AN:

4814

European-Finnish (FIN)

AF:

0.829

AC:

8755

AN:

10564

Middle Eastern (MID)

AF:

0.748

AC:

220

AN:

294

European-Non Finnish (NFE)

AF:

0.840

AC:

57099

AN:

67968

Other (OTH)

AF:

0.688

AC:

1451

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1239

2478

3718

4957

6196

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

780

1560

2340

3120

3900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.743

Hom.:

5586

Bravo

AF:

0.642

Asia WGS

AF:

0.838

AC:

2915

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

0.16

(source)

DANN

Benign

0.73

PhyloP100

-1.5

PromoterAI

-0.0070

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over