chr8-71315372-G-A

Variant names:

• chr8-71315372-G-A
• rs10094908
• NM_000503.6:c.556+2180C>T

Variant summary

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

The NM_000503.6(EYA1):​c.556+2180C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,124 control chromosomes in the GnomAD database, including 3,020 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 0.19 (3020 hom., cov: 33)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 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.556+2180C>T		intron	N/A	NP_000494.2
	EYA1	NM_001370333.1		c.643+2180C>T		intron	N/A	NP_001357262.1
	EYA1	NM_001370334.1		c.556+2180C>T		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.556+2180C>T		intron	N/A	ENSP00000342626.3
	EYA1	ENST00000388742.8	TSL:1	c.556+2180C>T		intron	N/A	ENSP00000373394.4
	EYA1	ENST00000419131.6	TSL:1	c.541+2180C>T		intron	N/A	ENSP00000410176.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28192 AN: 152006 Hom.: 3023 Cov.: 33

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.111

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.170

Gnomad SAS AF: 0.184

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.176

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

GnomAD4 genome AF: 0.185 AC: 28184 AN: 152124 Hom.: 3020 Cov.: 33 AF XY: 0.184 AC XY: 13705 AN XY: 74354

African (AFR) AF: 0.101 AC: 4196 AN: 41542

American (AMR) AF: 0.150 AC: 2289 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 533 AN: 3470

East Asian (EAS) AF: 0.170 AC: 877 AN: 5160

South Asian (SAS) AF: 0.183 AC: 881 AN: 4824

European-Finnish (FIN) AF: 0.248 AC: 2626 AN: 10578

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.239 AC: 16269 AN: 67960

Other (OTH) AF: 0.178 AC: 377 AN: 2116

Alfa AF: 0.212 Hom.: 425

Bravo AF: 0.172

Asia WGS AF: 0.188 AC: 652 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.6
DANN	Benign	0.69
PhyloP100		0.087
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: rs10094908; hg19: chr8-72227607;