rs751948150

Positions:

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

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_004447.6(EPS8):​c.60-12_60-4delTTATTATTA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000343 in 1,083,710 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00035 (5 hom.)
• Consequence: EPS8 NM_004447.6 splice_region, intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.19

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 12-15681305-GTAATAATAA-G is Benign according to our data. Variant chr12-15681305-GTAATAATAA-G is described in ClinVar as [Likely_benign]. Clinvar id is 1218122.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000313 (46/146990) while in subpopulation NFE AF= 0.000464 (31/66822). AF 95% confidence interval is 0.000335. There are 0 homozygotes in gnomad4. There are 22 alleles in male gnomad4 subpopulation. Median coverage is 27. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EPS8	NM_004447.6	c.60-12_60-4delTTATTATTA		splice_region_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.60-12_60-4delTTATTATTA		splice_region_variant, intron_variant		1	NM_004447.6	ENSP00000281172.5

Frequencies

GnomAD3 genomes AF: 0.000313 AC: 46 AN: 146964 Hom.: 0 Cov.: 27

Gnomad AFR AF: 0.000226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000204

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000464

Gnomad OTH AF: 0.00150

GnomAD3 exomes AF: 0.000288 AC: 44 AN: 152932 Hom.: 1 AF XY: 0.000211 AC XY: 18 AN XY: 85482

Gnomad AFR exome AF: 0.000453

Gnomad AMR exome AF: 0.000339

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000591

Gnomad NFE exome AF: 0.000425

Gnomad OTH exome AF: 0.000327

GnomAD4 exome AF: 0.000348 AC: 326 AN: 936720 Hom.: 5 AF XY: 0.000324 AC XY: 153 AN XY: 471798

Gnomad4 AFR exome AF: 0.000355

Gnomad4 AMR exome AF: 0.000329

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000105

Gnomad4 SAS exome AF: 0.000246

Gnomad4 FIN exome AF: 0.000128

Gnomad4 NFE exome AF: 0.000376

Gnomad4 OTH exome AF: 0.000468

GnomAD4 genome AF: 0.000313 AC: 46 AN: 146990 Hom.: 0 Cov.: 27 AF XY: 0.000308 AC XY: 22 AN XY: 71500

Gnomad4 AFR AF: 0.000225

Gnomad4 AMR AF: 0.000203

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000464

Gnomad4 OTH AF: 0.00149

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	Labcorp Genetics (formerly Invitae), Labcorp	Aug 20, 2022	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 26, 2023	See Variant Classification Assertion Criteria. -

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;