8-71458942-G-T

Variant names:

• chr8-71458942-G-T
• rs12549296
• ENST00000523987.4:n.322+11916C>A

Variant summary

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

The NM_001370333.1(EYA1):​c.33+76802C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,090 control chromosomes in the GnomAD database, including 1,877 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 0.12 (1877 hom., cov: 32)
• Consequence: EYA1 NM_001370333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.102
• Publications: 0 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	NM_001370333.1		c.33+76802C>A		intron	N/A	NP_001357262.1	A0A2R8Y6K4
	EYA1	NM_001370334.1		c.-55+11916C>A		intron	N/A	NP_001357263.1	Q99502-1
	EYA1	NM_001370335.1		c.-55+70887C>A		intron	N/A	NP_001357264.1	Q99502-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EYA1	ENST00000523987.4	TSL:1	n.322+11916C>A		intron	N/A
	EYA1	ENST00000643681.1		c.33+76802C>A		intron	N/A	ENSP00000495390.1	A0A2R8Y6K4
	EYA1	ENST00000645793.1		c.-55+70887C>A		intron	N/A	ENSP00000496255.1	Q99502-1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17605 AN: 151972 Hom.: 1876 Cov.: 32

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0471

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.0413

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.113

Gnomad FIN AF: 0.0830

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0388

Gnomad OTH AF: 0.0967

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

GnomAD4 genome AF: 0.116 AC: 17630 AN: 152090 Hom.: 1877 Cov.: 32 AF XY: 0.123 AC XY: 9114 AN XY: 74328

African (AFR) AF: 0.161 AC: 6681 AN: 41498

American (AMR) AF: 0.265 AC: 4034 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.0413 AC: 143 AN: 3466

East Asian (EAS) AF: 0.478 AC: 2455 AN: 5140

South Asian (SAS) AF: 0.112 AC: 540 AN: 4818

European-Finnish (FIN) AF: 0.0830 AC: 880 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0388 AC: 2641 AN: 67998

Other (OTH) AF: 0.0967 AC: 204 AN: 2110

Alfa AF: 0.0348 Hom.: 32

Bravo AF: 0.137

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.13
DANN	Benign	0.62
PhyloP100		-0.10

Splicing

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

Other links and lift over

dbSNP: rs12549296; hg19: chr8-72371177;