12-15624079-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004447.6(EPS8):c.2225+148G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0362 in 554,852 control chromosomes in the GnomAD database, including 886 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.063 (588 hom., cov: 32)
  • Exomes 𝑓: 0.026 (298 hom.)
• Consequence: EPS8 NM_004447.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.90

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 12-15624079-C-G is Benign according to our data. Variant chr12-15624079-C-G is described in ClinVar as [Benign]. Clinvar id is 1284234.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPS8	NM_004447.6	c.2225+148G>C		intron_variant		ENST00000281172.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS8	ENST00000281172.10	c.2225+148G>C		intron_variant		1	NM_004447.6	P1

Frequencies

GnomAD3 genomes AF: 0.0628 AC: 9551 AN: 152140 Hom.: 588 Cov.: 32

Gnomad AFR AF: 0.169

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0147

Gnomad EAS AF: 0.0413

Gnomad SAS AF: 0.0460

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0211

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.0261 AC: 10514 AN: 402594 Hom.: 298 AF XY: 0.0262 AC XY: 5481 AN XY: 209336

Gnomad4 AFR exome AF: 0.168

Gnomad4 AMR exome AF: 0.0232

Gnomad4 ASJ exome AF: 0.0175

Gnomad4 EAS exome AF: 0.0299

Gnomad4 SAS exome AF: 0.0452

Gnomad4 FIN exome AF: 0.00513

Gnomad4 NFE exome AF: 0.0212

Gnomad4 OTH exome AF: 0.0337

GnomAD4 genome AF: 0.0628 AC: 9558 AN: 152258 Hom.: 588 Cov.: 32 AF XY: 0.0618 AC XY: 4601 AN XY: 74470

Gnomad4 AFR AF: 0.168

Gnomad4 AMR AF: 0.0316

Gnomad4 ASJ AF: 0.0147

Gnomad4 EAS AF: 0.0412

Gnomad4 SAS AF: 0.0458

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.0211

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0468 Hom.: 58

Bravo AF: 0.0695

Asia WGS AF: 0.0430 AC: 149 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.019
Dann	Benign	0.51

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: rs67319686; hg19: chr12-15777013;