1-216072702-G-A

Position:

• chr1-216072702-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_206933.4(USH2A):​c.5857+187C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.11 in 633,892 control chromosomes in the GnomAD database, including 8,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (5525 hom., cov: 32)
  • Exomes 𝑓: 0.085 (3059 hom.)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.119

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-AS2 (HGNC:40605): (USH2A antisense RNA 2)

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-216072702-G-A is Benign according to our data. Variant chr1-216072702-G-A is described in ClinVar as [Benign]. Clinvar id is 1247889.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.5857+187C>T		intron_variant		ENST00000307340.8
USH2A-AS2	NR_125992.1	n.136+102G>A		intron_variant, non_coding_transcript_variant
USH2A-AS2	NR_125993.1	n.136+102G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.5857+187C>T		intron_variant		1	NM_206933.4	P1
USH2A-AS2	ENST00000446411.5	n.136+102G>A		intron_variant, non_coding_transcript_variant		2
USH2A	ENST00000674083.1	c.5857+187C>T		intron_variant
USH2A-AS2	ENST00000430890.5			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.191 AC: 29035 AN: 151972 Hom.: 5495 Cov.: 32

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0732

Gnomad EAS AF: 0.0166

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0573

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0754

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.0845 AC: 40727 AN: 481804 Hom.: 3059 Cov.: 5 AF XY: 0.0821 AC XY: 21186 AN XY: 258148

Gnomad4 AFR exome AF: 0.492

Gnomad4 AMR exome AF: 0.0748

Gnomad4 ASJ exome AF: 0.0750

Gnomad4 EAS exome AF: 0.0120

Gnomad4 SAS exome AF: 0.0712

Gnomad4 FIN exome AF: 0.0629

Gnomad4 NFE exome AF: 0.0766

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.192 AC: 29126 AN: 152088 Hom.: 5525 Cov.: 32 AF XY: 0.185 AC XY: 13768 AN XY: 74344

Gnomad4 AFR AF: 0.494

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.0732

Gnomad4 EAS AF: 0.0164

Gnomad4 SAS AF: 0.0731

Gnomad4 FIN AF: 0.0573

Gnomad4 NFE AF: 0.0754

Gnomad4 OTH AF: 0.168

Alfa AF: 0.102 Hom.: 1846

Bravo AF: 0.208

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 07, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.33
DANN	Benign	0.14

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: rs17026017; hg19: chr1-216246044;