1-216196495-AT-A

Position:

• chr1-216196495-AT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_206933.4(USH2A):​c.4251+57del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00293 in 1,599,826 control chromosomes in the GnomAD database, including 130 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (66 hom.)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.303

Genes affected

USH2A (HGNC:12601): (usherin) This gene encodes a protein that contains laminin EGF motifs, a pentaxin domain, and many fibronectin type III motifs. The protein is found in the basement membrane, and may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa and retinitis pigmentosa. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2008]

USH2A-AS1 (HGNC:40606): (USH2A antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 1-216196495-AT-A is Benign according to our data. Variant chr1-216196495-AT-A is described in ClinVar as [Benign]. Clinvar id is 1245102.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.4251+57del		intron_variant		ENST00000307340.8
USH2A-AS1	XR_922596.4	n.691+571del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.4251+57del		intron_variant		1	NM_206933.4	P1
USH2A	ENST00000366942.3	c.4251+57del		intron_variant		1
USH2A-AS1	ENST00000420867.1	n.362+571del		intron_variant, non_coding_transcript_variant		3
USH2A	ENST00000674083.1	c.4251+57del		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2364 AN: 152142 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0521

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00622

GnomAD4 exome AF: 0.00160 AC: 2318 AN: 1447566 Hom.: 66 AF XY: 0.00138 AC XY: 997 AN XY: 720962

Gnomad4 AFR exome AF: 0.0589

Gnomad4 AMR exome AF: 0.00325

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000127

Gnomad4 OTH exome AF: 0.00303

GnomAD4 genome AF: 0.0155 AC: 2365 AN: 152260 Hom.: 64 Cov.: 32 AF XY: 0.0148 AC XY: 1105 AN XY: 74452

Gnomad4 AFR AF: 0.0520

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00616

Bravo AF: 0.0182

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

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: rs141989167; hg19: chr1-216369837;