chr12-15863174-T-C

Position:

• chr12-15863174-T-C

Variant summary

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

The XR_002957404.2(LOC102724146):​n.130-17734A>G variant causes a intron, non coding transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,154 control chromosomes in the GnomAD database, including 30,037 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 0.57 (30037 hom., cov: 33)
• Consequence: LOC102724146 XR_002957404.2 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.279

Genes affected

LOC102724146 (HGNC:):

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
LOC102724146	XR_002957404.2	n.130-17734A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EPS8	ENST00000535752.5	c.-22+17933A>G		intron_variant		4
EPS8	ENST00000646828.1	c.-336+17933A>G		intron_variant				P1
EPS8	ENST00000646918.1	c.-366+17933A>G		intron_variant				P1
EPS8	ENST00000647087.1	c.-174+17933A>G		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86787 AN: 152036 Hom.: 30043 Cov.: 33

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.677

Gnomad EAS AF: 0.768

Gnomad SAS AF: 0.804

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.589

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.570 AC: 86776 AN: 152154 Hom.: 30037 Cov.: 33 AF XY: 0.574 AC XY: 42688 AN XY: 74380

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.612

Gnomad4 ASJ AF: 0.677

Gnomad4 EAS AF: 0.768

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.711

Gnomad4 NFE AF: 0.753

Gnomad4 OTH AF: 0.591

Alfa AF: 0.706 Hom.: 15866

Bravo AF: 0.542

Asia WGS AF: 0.751 AC: 2613 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	8.6
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10846239; hg19: chr12-16016108; COSMIC: COSV101606206;