rs7006821

Variant names:

• chr8-71357847-T-C
• rs7006821
• NM_000503.6:c.-54-1336A>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.-54-1336A>G variant causes a intron change. The variant allele was found at a frequency of 0.0887 in 152,240 control chromosomes in the GnomAD database, including 789 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 0.089 (789 hom., cov: 33)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• Publications: 8 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 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.-54-1336A>G		intron	N/A	NP_000494.2
	EYA1	NM_001370333.1		c.34-1336A>G		intron	N/A	NP_001357262.1	A0A2R8Y6K4
	EYA1	NM_001370334.1		c.-54-1336A>G		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.-54-1336A>G		intron	N/A	ENSP00000342626.3	Q99502-1
	EYA1	ENST00000643681.1		c.34-1336A>G		intron	N/A	ENSP00000495390.1	A0A2R8Y6K4
	EYA1	ENST00000645793.1		c.-54-1336A>G		intron	N/A	ENSP00000496255.1	Q99502-1

Frequencies

GnomAD3 genomes AF: 0.0887 AC: 13491 AN: 152122 Hom.: 784 Cov.: 33

Gnomad AFR AF: 0.163

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0565

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.00520

Gnomad SAS AF: 0.0391

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0634

Gnomad OTH AF: 0.0837

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

GnomAD4 genome AF: 0.0887 AC: 13510 AN: 152240 Hom.: 789 Cov.: 33 AF XY: 0.0859 AC XY: 6397 AN XY: 74438

African (AFR) AF: 0.163 AC: 6786 AN: 41532

American (AMR) AF: 0.0563 AC: 861 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0594 AC: 206 AN: 3470

East Asian (EAS) AF: 0.00521 AC: 27 AN: 5182

South Asian (SAS) AF: 0.0394 AC: 190 AN: 4824

European-Finnish (FIN) AF: 0.0821 AC: 870 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0635 AC: 4316 AN: 68022

Other (OTH) AF: 0.0829 AC: 175 AN: 2112

Alfa AF: 0.0743 Hom.: 1064

Bravo AF: 0.0893

Asia WGS AF: 0.0270 AC: 94 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.64
PhyloP100		3.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7006821; hg19: chr8-72270082;