8-71214404-C-T

Variant names:

• chr8-71214404-C-T
• rs9298164
• NM_000503.6:c.1597+983G>A

Variant summary

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

The NM_000503.6(EYA1):​c.1597+983G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.327 in 152,072 control chromosomes in the GnomAD database, including 8,885 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 0.33 (8885 hom., cov: 32)
• Consequence: EYA1 NM_000503.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.213
• Publications: 2 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

ENSG00000285579 (HGNC:):

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 (EAS) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
EYA1	NM_000503.6	c.1597+983G>A		intron_variant	Intron 16 of 17	ENST00000340726.8	NP_000494.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000340726.8	c.1597+983G>A		intron_variant	Intron 16 of 17	1	NM_000503.6	ENSP00000342626.3

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49646 AN: 151954 Hom.: 8868 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.416

Gnomad ASJ AF: 0.340

Gnomad EAS AF: 0.754

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.368

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.295

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.327 AC: 49701 AN: 152072 Hom.: 8885 Cov.: 32 AF XY: 0.335 AC XY: 24883 AN XY: 74338

African (AFR) AF: 0.261 AC: 10853 AN: 41504

American (AMR) AF: 0.417 AC: 6364 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.340 AC: 1182 AN: 3472

East Asian (EAS) AF: 0.755 AC: 3897 AN: 5164

South Asian (SAS) AF: 0.469 AC: 2261 AN: 4816

European-Finnish (FIN) AF: 0.368 AC: 3883 AN: 10550

Middle Eastern (MID) AF: 0.313 AC: 92 AN: 294

European-Non Finnish (NFE) AF: 0.295 AC: 20072 AN: 67974

Other (OTH) AF: 0.337 AC: 711 AN: 2112

Alfa AF: 0.311 Hom.: 33851

Bravo AF: 0.330

Asia WGS AF: 0.616 AC: 2145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.51
DANN	Benign	0.42
PhyloP100		-0.21
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: rs9298164; hg19: chr8-72126639;