12-15681305-G-GTAATAATAATAA

Position:

• chr12-15681305-G-GTAATAATAATAA

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_004447.6(EPS8):​c.60-4_60-3insTTATTATTATTA variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00112 in 146,992 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00020 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: EPS8 NM_004447.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.197

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 -12 ACMG points.

• BP6: Variant 12-15681305-G-GTAATAATAATAA is Benign according to our data. Variant chr12-15681305-G-GTAATAATAATAA is described in ClinVar as [Likely_benign]. Clinvar id is 513294.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00112 (165/146992) while in subpopulation AFR AF= 0.0024 (96/39964). AF 95% confidence interval is 0.00201. There are 0 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EPS8	NM_004447.6	c.60-4_60-3insTTATTATTATTA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000281172.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS8	ENST00000281172.10	c.60-4_60-3insTTATTATTATTA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004447.6	P1

Frequencies

GnomAD3 genomes AF: 0.00112 AC: 164 AN: 146964 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.00238

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.000215

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000763

Gnomad OTH AF: 0.000500

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000205 AC: 192 AN: 936854 Hom.: 0 Cov.: 11 AF XY: 0.000214 AC XY: 101 AN XY: 471860

Gnomad4 AFR exome AF: 0.000947

Gnomad4 AMR exome AF: 0.000123

Gnomad4 ASJ exome AF: 0.0000590

Gnomad4 EAS exome AF: 0.0000699

Gnomad4 SAS exome AF: 0.0000821

Gnomad4 FIN exome AF: 0.0000514

Gnomad4 NFE exome AF: 0.000210

Gnomad4 OTH exome AF: 0.000260

GnomAD4 genome AF: 0.00112 AC: 165 AN: 146992 Hom.: 0 Cov.: 27 AF XY: 0.000993 AC XY: 71 AN XY: 71502

Gnomad4 AFR AF: 0.00240

Gnomad4 AMR AF: 0.00102

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000197

Gnomad4 SAS AF: 0.000216

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000763

Gnomad4 OTH AF: 0.000497

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 03, 2019	- -
Likely benign, criteria provided, single submitter	clinical testing	Invitae	Dec 22, 2023	- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs201331879; hg19: chr12-15834239;