1-28000058-C-A

Variant names:

• chr1-28000058-C-A
• rs375368234
• NM_001990.4:c.994-9G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001990.4(EYA3):​c.994-9G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,426,674 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: EYA3 NM_001990.4 intron
• Scores: Splicing: ADA: 0.00003740
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.426
• Publications: 0 publications found

Genes affected

EYA3 (HGNC:3521): (EYA transcriptional coactivator and phosphatase 3) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may act as a transcriptional activator and have a role during development. It can act as a mediator of chemoresistance and cell survival in Ewing sarcoma cells, where this gene is up-regulated via a micro-RNA that binds to the 3' UTR of the transcript. A similar protein in mice acts as a transcriptional activator. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Sep 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001990.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA3	NM_001990.4	MANE Select	c.994-9G>T		intron	N/A	NP_001981.2
	EYA3	NM_001282560.2		c.856-9G>T		intron	N/A	NP_001269489.1	Q99504-3
	EYA3	NM_001282561.2		c.856-9G>T		intron	N/A	NP_001269490.1	Q99504-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA3	ENST00000373871.8	TSL:1 MANE Select	c.994-9G>T		intron	N/A	ENSP00000362978.3	Q99504-1
	EYA3	ENST00000373863.3	TSL:1	c.856-9G>T		intron	N/A	ENSP00000362970.3	Q99504-3
	EYA3	ENST00000471498.5	TSL:1	n.1136-9G>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1426674 Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0 AN XY: 709614

African (AFR) AF: 0.00 AC: 0 AN: 31540

American (AMR) AF: 0.00 AC: 0 AN: 37140

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25062

East Asian (EAS) AF: 0.00 AC: 0 AN: 38522

South Asian (SAS) AF: 0.00 AC: 0 AN: 79420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097282

Other (OTH) AF: 0.0000170 AC: 1 AN: 58988

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.2
DANN	Benign	0.61
PhyloP100		-0.43

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs375368234; hg19: chr1-28326569;