rs10103397

Variant names:

• chr8-71199364-A-G
• rs10103397
• NM_000503.6:c.1755T>C

Your query was ambiguous. Multiple possible variants found:

• chr8-71199364-A-G
• chr8-71199364-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000503.6(EYA1):​c.1755T>C​(p.His585His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 1,610,680 control chromosomes in the GnomAD database, including 100,999 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.36 (10508 hom., cov: 32)
  • Exomes 𝑓: 0.34 (90491 hom.)
• Consequence: EYA1 NM_000503.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:14
• Conservation: PhyloP100: -0.426
• Publications: 28 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 8-71199364-A-G is Benign according to our data. Variant chr8-71199364-A-G is described in ClinVar as Benign. ClinVar VariationId is 48107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.426 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

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.1755T>C	p.His585His	synonymous	Exon 18 of 18	NP_000494.2
	EYA1	NM_001370333.1		c.1842T>C	p.His614His	synonymous	Exon 19 of 19	NP_001357262.1	A0A2R8Y6K4
	EYA1	NM_001370334.1		c.1755T>C	p.His585His	synonymous	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.1755T>C	p.His585His	synonymous	Exon 18 of 18	ENSP00000342626.3	Q99502-1
	EYA1	ENST00000388742.8	TSL:1	c.1755T>C	p.His585His	synonymous	Exon 17 of 17	ENSP00000373394.4	Q99502-1
	EYA1	ENST00000419131.6	TSL:1	c.1650T>C	p.His550His	synonymous	Exon 16 of 16	ENSP00000410176.1	Q99502-3

Frequencies

GnomAD3 genomes AF: 0.360 AC: 54678 AN: 151900 Hom.: 10476 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.350

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.303

Gnomad OTH AF: 0.360

GnomAD2 exomes AF: 0.396 AC: 98291 AN: 248410 AF XY: 0.389

Gnomad AFR exome AF: 0.350

Gnomad AMR exome AF: 0.523

Gnomad ASJ exome AF: 0.353

Gnomad EAS exome AF: 0.780

Gnomad FIN exome AF: 0.345

Gnomad NFE exome AF: 0.299

Gnomad OTH exome AF: 0.358

GnomAD4 exome AF: 0.339 AC: 493791 AN: 1458662 Hom.: 90491 Cov.: 32 AF XY: 0.340 AC XY: 246908 AN XY: 725630

African (AFR) AF: 0.352 AC: 11778 AN: 33426

American (AMR) AF: 0.513 AC: 22897 AN: 44612

Ashkenazi Jewish (ASJ) AF: 0.357 AC: 9323 AN: 26116

East Asian (EAS) AF: 0.784 AC: 31050 AN: 39620

South Asian (SAS) AF: 0.449 AC: 38651 AN: 86026

European-Finnish (FIN) AF: 0.339 AC: 17883 AN: 52778

Middle Eastern (MID) AF: 0.304 AC: 1750 AN: 5764

European-Non Finnish (NFE) AF: 0.305 AC: 338892 AN: 1110010

Other (OTH) AF: 0.358 AC: 21567 AN: 60310

GnomAD4 genome AF: 0.360 AC: 54766 AN: 152018 Hom.: 10508 Cov.: 32 AF XY: 0.368 AC XY: 27327 AN XY: 74320

African (AFR) AF: 0.354 AC: 14667 AN: 41420

American (AMR) AF: 0.439 AC: 6712 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 1215 AN: 3468

East Asian (EAS) AF: 0.778 AC: 4027 AN: 5178

South Asian (SAS) AF: 0.484 AC: 2335 AN: 4820

European-Finnish (FIN) AF: 0.370 AC: 3911 AN: 10558

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.303 AC: 20615 AN: 67982

Other (OTH) AF: 0.368 AC: 775 AN: 2108

Alfa AF: 0.315 Hom.: 2628

Bravo AF: 0.366

Asia WGS AF: 0.637 AC: 2215 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	2	Branchiootic syndrome 1 (2)
-	-	2	not provided (2)
-	-	2	Otofaciocervical syndrome 1 (2)
-	-	1	Branchiootorenal syndrome 1 (1)
-	-	1	Melnick-Fraser syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-0.43
Mutation Taster		=99/1	polymorphism (auto)

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: rs10103397; hg19: chr8-72111599; COSMIC: COSV100378647;