chr8-71198117-TTAA-T

Position:

• chr8-71198117-TTAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000503.6(EYA1):​c.*1220_*1222del 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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 491 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
EYA1	NM_000503.6	c.*1220_*1222del		3_prime_UTR_variant	18/18	ENST00000340726.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
EYA1	ENST00000340726.8	c.*1220_*1222del		3_prime_UTR_variant	18/18	1	NM_000503.6	P4
	ENST00000521685.5	n.271-1018_271-1016del		intron_variant, non_coding_transcript_variant		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

Gnomad4 FIN exome AF: 0.00775

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.000529

Gnomad4 AMR AF: 0.0241

Gnomad4 ASJ AF: 0.0101

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00292

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00248 Hom.: 1

Bravo AF: 0.00444

Asia WGS AF: 0.00289 AC: 10 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Otofaciocervical syndrome 1 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Branchiootorenal Spectrum Disorders Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs574723016; hg19: chr8-72110352;