12-15623289-TAAAAA-TAAAAAAAAA

Variant names:

• chr12-15623289-T-TAAAA
• NM_004447.6:c.2226-6_2226-3dupTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_004447.6(EPS8):​c.2226-6_2226-3dupTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000251 in 1,197,220 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000025 (0 hom.)
• Consequence: EPS8 NM_004447.6 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00600

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.00000251 (3/1197220) while in subpopulation AFR AF= 0.0000733 (2/27302). AF 95% confidence interval is 0.0000121. There are 0 homozygotes in gnomad4_exome. There are 1 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EPS8	NM_004447.6	c.2226-6_2226-3dupTTTT		splice_region_variant, intron_variant	Intron 19 of 20	ENST00000281172.10	NP_004438.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EPS8	ENST00000281172.10	c.2226-3_2226-2insTTTT		splice_region_variant, intron_variant	Intron 19 of 20	1	NM_004447.6	ENSP00000281172.5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000251 AC: 3 AN: 1197220 Hom.: 0 Cov.: 0 AF XY: 0.00000167 AC XY: 1 AN XY: 598526

Gnomad4 AFR exome AF: 0.0000733

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000109

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-15776223;