rs751948150

Positions:

• chr12-15681305-G-GTAATAA
• chr12-15681305-G-GTAATAATAATAATAA
• chr12-15681305-G-GTAATAATAATAATAATAATAA
• chr12-15681305-GTAATAA-G
• chr12-15681305-G-GTAA
• chr12-15681305-G-GTAATAATAATAATAATAA
• chr12-15681305-GTAATAATAA-G
• chr12-15681305-GTAATAATAATAATAA-G
• chr12-15681305-G-GTAATAATAATAA
• chr12-15681305-GTAATAATAATAA-G
• chr12-15681305-GTAA-G
• chr12-15681305-G-GTAATAATAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_004447.6(EPS8):​c.60-4_60-3insTTATTA 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 0.0288 in 1,083,108 control chromosomes in the GnomAD database, including 741 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (417 hom., cov: 27)
  • Exomes 𝑓: 0.022 (324 hom.)
• Consequence: EPS8 NM_004447.6 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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 -16 ACMG points.

• BP6: Variant 12-15681305-G-GTAATAA is Benign according to our data. Variant chr12-15681305-G-GTAATAA is described in ClinVar as [Benign]. Clinvar id is 517824.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8	NM_004447.6	c.60-4_60-3insTTATTA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000281172.10	NP_004438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10	c.60-4_60-3insTTATTA		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_004447.6	ENSP00000281172	P1

Frequencies

GnomAD3 genomes AF: 0.0692 AC: 10160 AN: 146876 Hom.: 416 Cov.: 27

Gnomad AFR AF: 0.0906

Gnomad AMI AF: 0.0852

Gnomad AMR AF: 0.0568

Gnomad ASJ AF: 0.0769

Gnomad EAS AF: 0.0365

Gnomad SAS AF: 0.0157

Gnomad FIN AF: 0.0713

Gnomad MID AF: 0.0654

Gnomad NFE AF: 0.0642

Gnomad OTH AF: 0.0766

GnomAD3 exomes AF: 0.0179 AC: 2732 AN: 152932 Hom.: 29 AF XY: 0.0175 AC XY: 1498 AN XY: 85482

Gnomad AFR exome AF: 0.0104

Gnomad AMR exome AF: 0.00515

Gnomad ASJ exome AF: 0.0423

Gnomad EAS exome AF: 0.00369

Gnomad SAS exome AF: 0.00931

Gnomad FIN exome AF: 0.0482

Gnomad NFE exome AF: 0.0163

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0224 AC: 21012 AN: 936204 Hom.: 324 Cov.: 11 AF XY: 0.0237 AC XY: 11152 AN XY: 471520

Gnomad4 AFR exome AF: 0.0413

Gnomad4 AMR exome AF: 0.0135

Gnomad4 ASJ exome AF: 0.0433

Gnomad4 EAS exome AF: 0.0139

Gnomad4 SAS exome AF: 0.00739

Gnomad4 FIN exome AF: 0.0422

Gnomad4 NFE exome AF: 0.0218

Gnomad4 OTH exome AF: 0.0238

GnomAD4 genome AF: 0.0692 AC: 10165 AN: 146904 Hom.: 417 Cov.: 27 AF XY: 0.0694 AC XY: 4960 AN XY: 71466

Gnomad4 AFR AF: 0.0908

Gnomad4 AMR AF: 0.0566

Gnomad4 ASJ AF: 0.0769

Gnomad4 EAS AF: 0.0365

Gnomad4 SAS AF: 0.0155

Gnomad4 FIN AF: 0.0713

Gnomad4 NFE AF: 0.0642

Gnomad4 OTH AF: 0.0757

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Mar 21, 2019	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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;