rs4343077

chr12-15780257-G-A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPS8	NM_004447.6	c.-22+8904C>T		intron_variant		ENST00000281172.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS8	ENST00000281172.10	c.-22+8904C>T		intron_variant		1	NM_004447.6	P1
	ENST00000544015.1	n.83+107G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102232 AN: 151782 Hom.: 38818 Cov.: 30

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: 6 AN: 8 Hom.: 3 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.673 AC: 102230 AN: 151900 Hom.: 38807 Cov.: 30 AF XY: 0.677 AC XY: 50291 AN XY: 74268

Gnomad4 AFR AF: 0.298

Gnomad4 AMR AF: 0.681

Gnomad4 ASJ AF: 0.764

Gnomad4 EAS AF: 0.861

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.829

Gnomad4 NFE AF: 0.840

Gnomad4 OTH AF: 0.688

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
Dann	Benign	0.73

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: rs4343077; hg19: chr12-15933191;