8-71382353-G-A

Variant names:

• chr8-71382353-G-A
• rs10957550
• NM_001370333.1:c.34-25842C>T

Variant summary

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

The NM_001370333.1(EYA1):​c.34-25842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,830 control chromosomes in the GnomAD database, including 6,372 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 0.27 (6372 hom., cov: 32)
• Consequence: EYA1 NM_001370333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370333.1. 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_001370333.1		c.34-25842C>T		intron	N/A	NP_001357262.1
	EYA1	NM_001370334.1		c.-54-25842C>T		intron	N/A	NP_001357263.1
	EYA1	NM_001370335.1		c.-54-25842C>T		intron	N/A	NP_001357264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	ENST00000643681.1		c.34-25842C>T		intron	N/A	ENSP00000495390.1
	EYA1	ENST00000645793.1		c.-54-25842C>T		intron	N/A	ENSP00000496255.1
	EYA1	ENST00000647540.1		c.-54-25842C>T		intron	N/A	ENSP00000494438.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40953 AN: 151710 Hom.: 6369 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.270 AC: 40969 AN: 151830 Hom.: 6372 Cov.: 32 AF XY: 0.274 AC XY: 20311 AN XY: 74170

African (AFR) AF: 0.165 AC: 6828 AN: 41480

American (AMR) AF: 0.325 AC: 4953 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1118 AN: 3470

East Asian (EAS) AF: 0.705 AC: 3642 AN: 5164

South Asian (SAS) AF: 0.400 AC: 1925 AN: 4808

European-Finnish (FIN) AF: 0.240 AC: 2524 AN: 10500

Middle Eastern (MID) AF: 0.241 AC: 69 AN: 286

European-Non Finnish (NFE) AF: 0.280 AC: 18983 AN: 67850

Other (OTH) AF: 0.300 AC: 632 AN: 2110

Alfa AF: 0.236 Hom.: 1528

Bravo AF: 0.274

Asia WGS AF: 0.530 AC: 1814 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.60
PhyloP100		0.88

Splicing

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

Other links and lift over

dbSNP: rs10957550; hg19: chr8-72294588;