rs10957550

Positions:

• chr8-71382353-G-A
• chr8-71382353-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001370333.1(EYA1):​c.34-25842C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,830 control chromosomes in the GnomAD database, including 6,372 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 0.27 (6372 hom., cov: 32)
• Consequence: EYA1 NM_001370333.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.879

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA1	NM_001370333.1	c.34-25842C>T		intron_variant			NP_001357262.1
EYA1	NM_001370334.1	c.-54-25842C>T		intron_variant			NP_001357263.1
EYA1	NM_001370335.1	c.-54-25842C>T		intron_variant			NP_001357264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000643681.1	c.34-25842C>T		intron_variant				ENSP00000495390
EYA1	ENST00000644229.1	c.34-25842C>T		intron_variant				ENSP00000494568
EYA1	ENST00000644712.1	c.34-25842C>T		intron_variant				ENSP00000496188

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40953 AN: 151710 Hom.: 6369 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.280

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.270 AC: 40969 AN: 151830 Hom.: 6372 Cov.: 32 AF XY: 0.274 AC XY: 20311 AN XY: 74170

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.705

Gnomad4 SAS AF: 0.400

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.280

Gnomad4 OTH AF: 0.300

Alfa AF: 0.233 Hom.: 1358

Bravo AF: 0.274

Asia WGS AF: 0.530 AC: 1814 AN: 3422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	11
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10957550; hg19: chr8-72294588;