rs574723016

Variant names:

• chr8-71198117-TTAA-T
• rs574723016
• NM_000503.6:c.*1220_*1222delTTA

Your query was ambiguous. Multiple possible variants found:

• chr8-71198117-TTAA-T
• chr8-71198117-TTAA-TTAATAA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000503.6(EYA1):​c.*1220_*1222delTTA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00323 in 152,580 control chromosomes in the GnomAD database, including 6 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0032 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0077 (0 hom.)
• Consequence: EYA1 NM_000503.6 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.00
• 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

ENSG00000254031 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 8-71198117-TTAA-T is Benign according to our data. Variant chr8-71198117-TTAA-T is described in ClinVar as Likely_benign. ClinVar VariationId is 363631.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00322 (491/152320) while in subpopulation AMR AF = 0.0241 (369/15300). AF 95% confidence interval is 0.0221. There are 6 homozygotes in GnomAd4. There are 261 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 491 AD gene.

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.*1220_*1222delTTA		3_prime_UTR	Exon 18 of 18	NP_000494.2
	EYA1	NM_001370333.1		c.*1220_*1222delTTA		3_prime_UTR	Exon 19 of 19	NP_001357262.1	A0A2R8Y6K4
	EYA1	NM_001370334.1		c.*1220_*1222delTTA		3_prime_UTR	Exon 20 of 20	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.*1220_*1222delTTA		3_prime_UTR	Exon 18 of 18	ENSP00000342626.3	Q99502-1
	EYA1	ENST00000388742.8	TSL:1	c.*1220_*1222delTTA		3_prime_UTR	Exon 17 of 17	ENSP00000373394.4	Q99502-1
	EYA1	ENST00000419131.6	TSL:1	c.*1220_*1222delTTA		3_prime_UTR	Exon 16 of 16	ENSP00000410176.1	Q99502-3

Frequencies

GnomAD3 genomes AF: 0.00320 AC: 487 AN: 152202 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0101

Gnomad EAS AF: 0.000384

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00292

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00670

GnomAD4 exome AF: 0.00769 AC: 2 AN: 260 Hom.: 0 AF XY: 0.00610 AC XY: 1 AN XY: 164

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00775 AC: 2 AN: 258

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.00322 AC: 491 AN: 152320 Hom.: 6 Cov.: 32 AF XY: 0.00350 AC XY: 261 AN XY: 74486

African (AFR) AF: 0.000529 AC: 22 AN: 41562

American (AMR) AF: 0.0241 AC: 369 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0101 AC: 35 AN: 3472

East Asian (EAS) AF: 0.000385 AC: 2 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00292 AC: 31 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68026

Other (OTH) AF: 0.00616 AC: 13 AN: 2112

Alfa AF: 0.00248 Hom.: 1

Bravo AF: 0.00444

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Branchiootorenal Spectrum Disorders (1)
-	-	1	Otofaciocervical syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=100/0	polymorphism

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: rs574723016; hg19: chr8-72110352;