dbSNP rs2218488: EYA1:c.124+3061G>T (chr8-71351721-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is The variant received 0 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Moderate

The NM_000503.6(EYA1):c.124+3061G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Splicing prediction tools (SpliceAI) predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

EYA1
NM_000503.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.17

Publications

16 publications found

Variant links:

Genes affected

EYA1 (HGNC:3519): (EYA transcriptional coactivator and phosphatase 1) This gene encodes a member of the eyes absent (EYA) family of proteins. The encoded protein may play a role in the developing kidney, branchial arches, eye, and ear. Mutations of this gene have been associated with branchiootorenal dysplasia syndrome, branchiootic syndrome, and sporadic cases of congenital cataracts and ocular anterior segment anomalies. A similar protein in mice can act as a transcriptional activator. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Dec 2013]

EYA1 Gene-Disease associations (from GenCC):

branchio-oto-renal syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, PanelApp Australia, Orphanet
branchiootorenal syndrome 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
branchiootic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

EYA1 links:

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new If you want to explore the variant's impact on the transcript NM_000503.6, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

Classification according to ACMG Germline Pathogenicity v2019

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 points.

PM2

Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD/XL) (threshold 0.0001) — PM2 moderate.

BP4

Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); Splicing verdict: benign (Strong).; Germline computational verdict: benign (Moderate).

Variant Effect in Transcripts

Automated classification analysis was done for transcript: NM_000503.6. You can select a different transcript below to see updated classification assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYA1	NM_000503.6	MANE Select	c.124+3061G>T	intron	N/A	NP_000494.2
EYA1	NM_001370333.1		c.211+3061G>T	intron	N/A	NP_001357262.1	A0A2R8Y6K4
EYA1	NM_001370334.1		c.124+3061G>T	intron	N/A	NP_001357263.1	Q99502-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EYA1	ENST00000340726.8	TSL:1 MANE Select	c.124+3061G>T	intron	N/A	ENSP00000342626.3	Q99502-1
EYA1	ENST00000388742.8	TSL:1	c.124+3061G>T	intron	N/A	ENSP00000373394.4	Q99502-1
EYA1	ENST00000419131.6	TSL:1	c.124+3061G>T	intron	N/A	ENSP00000410176.1	Q99502-3

Frequencies

GnomAD3 genomes

Cov.:

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.72

PhyloP100

1.2

AlphaGenome AVI

Uncertain

(source)

GPN-Star LLR

-0.21

(source)

GPN-Star score

0.21

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Pangolin (max)

Benign

0.0

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

Classification according to ACMG Germline Pathogenicity v2019

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over