rs6989867

Variant names:

• chr8-71283083-A-G
• rs6989867
• NM_000503.6:c.827-11186T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-71283083-A-G
• chr8-71283083-A-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.827-11186T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 151,850 control chromosomes in the GnomAD database, including 4,679 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 0.24 (4679 hom., cov: 31)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.335
• Publications: 6 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: Orphanet, ClinGen
• branchiootorenal syndrome 1

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.283 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	NM_000503.6	MANE Select	c.827-11186T>C		intron	N/A	NP_000494.2
	EYA1	NM_001370333.1		c.914-11186T>C		intron	N/A	NP_001357262.1	A0A2R8Y6K4
	EYA1	NM_001370334.1		c.827-11186T>C		intron	N/A	NP_001357263.1	Q99502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	ENST00000340726.8	TSL:1 MANE Select	c.827-11186T>C		intron	N/A	ENSP00000342626.3	Q99502-1
	EYA1	ENST00000388742.8	TSL:1	c.827-11186T>C		intron	N/A	ENSP00000373394.4	Q99502-1
	EYA1	ENST00000419131.6	TSL:1	c.812-11186T>C		intron	N/A	ENSP00000410176.1	Q99502-3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 36012 AN: 151732 Hom.: 4677 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.248

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.278

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.278

Gnomad OTH AF: 0.238

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

GnomAD4 genome AF: 0.237 AC: 36029 AN: 151850 Hom.: 4679 Cov.: 31 AF XY: 0.238 AC XY: 17664 AN XY: 74182

African (AFR) AF: 0.128 AC: 5281 AN: 41410

American (AMR) AF: 0.290 AC: 4428 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.248 AC: 859 AN: 3460

East Asian (EAS) AF: 0.274 AC: 1415 AN: 5156

South Asian (SAS) AF: 0.278 AC: 1341 AN: 4818

European-Finnish (FIN) AF: 0.269 AC: 2829 AN: 10508

Middle Eastern (MID) AF: 0.238 AC: 70 AN: 294

European-Non Finnish (NFE) AF: 0.278 AC: 18915 AN: 67930

Other (OTH) AF: 0.238 AC: 500 AN: 2102

Alfa AF: 0.224 Hom.: 1649

Bravo AF: 0.233

Asia WGS AF: 0.270 AC: 940 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.1
DANN	Benign	0.58
PhyloP100		0.34
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: rs6989867; hg19: chr8-72195318;