8-71458942-G-T

Position:

• chr8-71458942-G-T

Variant summary

Our verdict is Benign. Variant got -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

Genes affected

EYA1 (HGNC:):

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
EYA1	NM_001370333.1	c.33+76802C>A		intron_variant			NP_001357262.1
EYA1	NM_001370334.1	c.-55+11916C>A		intron_variant			NP_001357263.1
EYA1	NM_001370335.1	c.-55+70887C>A		intron_variant			NP_001357264.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
EYA1	ENST00000523987.4	n.322+11916C>A		intron_variant		1
EYA1	ENST00000643681.1	c.33+76802C>A		intron_variant				ENSP00000495390.1
EYA1	ENST00000645793.1	c.-55+70887C>A		intron_variant				ENSP00000496255.1

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

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.265

Gnomad4 ASJ AF: 0.0413

Gnomad4 EAS AF: 0.478

Gnomad4 SAS AF: 0.112

Gnomad4 FIN AF: 0.0830

Gnomad4 NFE AF: 0.0388

Gnomad4 OTH AF: 0.0967

Alfa AF: 0.0308 Hom.: 26

Bravo AF: 0.137

Asia WGS AF: 0.262 AC: 910 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs12549296; hg19: chr8-72371177;