chr8-71198118-T-G

Variant names:

• chr8-71198118-T-G
• rs117394899
• NM_000503.6:c.*1222A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_000503.6(EYA1):​c.*1222A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0139 in 151,630 control chromosomes in the GnomAD database, including 33 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.014 (33 hom., cov: 32)
  • Exomes 𝑓: 0.011 (0 hom.)
• Consequence: EYA1 NM_000503.6 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.00
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 8-71198118-T-G is Benign according to our data. Variant chr8-71198118-T-G is described in ClinVar as Benign. ClinVar VariationId is 363632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0139 (2110/151366) while in subpopulation NFE AF = 0.0213 (1449/67988). AF 95% confidence interval is 0.0204. There are 33 homozygotes in GnomAd4. There are 991 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2110 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.*1222A>C		3_prime_UTR	Exon 18 of 18	NP_000494.2
	EYA1	NM_001370333.1		c.*1222A>C		3_prime_UTR	Exon 19 of 19	NP_001357262.1	A0A2R8Y6K4
	EYA1	NM_001370334.1		c.*1222A>C		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.*1222A>C		3_prime_UTR	Exon 18 of 18	ENSP00000342626.3	Q99502-1
	EYA1	ENST00000388742.8	TSL:1	c.*1222A>C		3_prime_UTR	Exon 17 of 17	ENSP00000373394.4	Q99502-1
	EYA1	ENST00000419131.6	TSL:1	c.*1222A>C		3_prime_UTR	Exon 16 of 16	ENSP00000410176.1	Q99502-3

Frequencies

GnomAD3 genomes AF: 0.0140 AC: 2115 AN: 151256 Hom.: 33 Cov.: 32

Gnomad AFR AF: 0.00415

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.0347

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0145

Gnomad FIN AF: 0.00833

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0213

Gnomad OTH AF: 0.0145

GnomAD4 exome AF: 0.0114 AC: 3 AN: 264 Hom.: 0 Cov.: 0 AF XY: 0.0119 AC XY: 2 AN XY: 168

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: 0.0115 AC: 3 AN: 262

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: 0.0139 AC: 2110 AN: 151366 Hom.: 33 Cov.: 32 AF XY: 0.0134 AC XY: 991 AN XY: 73982

African (AFR) AF: 0.00417 AC: 173 AN: 41528

American (AMR) AF: 0.0115 AC: 167 AN: 14576

Ashkenazi Jewish (ASJ) AF: 0.0347 AC: 118 AN: 3402

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0141 AC: 68 AN: 4828

European-Finnish (FIN) AF: 0.00833 AC: 88 AN: 10560

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1449 AN: 67988

Other (OTH) AF: 0.0144 AC: 30 AN: 2088

Alfa AF: 0.0172 Hom.: 3

Bravo AF: 0.0136

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Branchiootic syndrome 1 (1)
-	-	1	Otofaciocervical syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	5.4
DANN	Benign	0.70
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: rs117394899; hg19: chr8-72110353;