rs2380716

Variant names:

• chr8-71262179-T-C
• rs2380716
• NM_000503.6:c.1050+7561A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000503.6(EYA1):​c.1050+7561A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 152,166 control chromosomes in the GnomAD database, including 1,117 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 0.12 (1117 hom., cov: 32)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.510
• Publications: 4 publications found

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, SUPPORTIVE Submitted by: ClinGen, Orphanet
• branchiootorenal syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• branchiootic syndrome 1

  Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
• branchiootic syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Variant Effect in Transcripts

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

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	NM_000503.6	MANE Select	c.1050+7561A>G		intron	N/A	NP_000494.2
	EYA1	NM_001370333.1		c.1137+7561A>G		intron	N/A	NP_001357262.1
	EYA1	NM_001370334.1		c.1050+7561A>G		intron	N/A	NP_001357263.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	ENST00000340726.8	TSL:1 MANE Select	c.1050+7561A>G		intron	N/A	ENSP00000342626.3
	EYA1	ENST00000388742.8	TSL:1	c.1050+7561A>G		intron	N/A	ENSP00000373394.4
	EYA1	ENST00000419131.6	TSL:1	c.1035+7561A>G		intron	N/A	ENSP00000410176.1

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17758 AN: 152048 Hom.: 1117 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.151

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.0704

Gnomad SAS AF: 0.0823

Gnomad FIN AF: 0.0964

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.0920

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

GnomAD4 genome AF: 0.117 AC: 17770 AN: 152166 Hom.: 1117 Cov.: 32 AF XY: 0.114 AC XY: 8465 AN XY: 74388

African (AFR) AF: 0.133 AC: 5537 AN: 41516

American (AMR) AF: 0.0719 AC: 1098 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 300 AN: 3472

East Asian (EAS) AF: 0.0704 AC: 364 AN: 5170

South Asian (SAS) AF: 0.0824 AC: 397 AN: 4818

European-Finnish (FIN) AF: 0.0964 AC: 1021 AN: 10590

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.128 AC: 8715 AN: 68006

Other (OTH) AF: 0.0910 AC: 192 AN: 2110

Alfa AF: 0.120 Hom.: 625

Bravo AF: 0.115

Asia WGS AF: 0.0690 AC: 241 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.48
PhyloP100		-0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs2380716; hg19: chr8-72174414;