rs17026635

Positions:

• chr1-216379025-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_206933.4(USH2A):​c.652-13940G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 152,110 control chromosomes in the GnomAD database, including 2,829 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 0.11 (2829 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.652-13940G>A		intron_variant		ENST00000307340.8
USH2A	NM_007123.6	c.652-13940G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.652-13940G>A		intron_variant		1	NM_206933.4	P1
USH2A	ENST00000366942.3	c.652-13940G>A		intron_variant		1
USH2A	ENST00000674083.1	c.652-13940G>A		intron_variant

Frequencies

GnomAD3 genomes AF: 0.112 AC: 17027 AN: 151992 Hom.: 2817 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.0230

Gnomad AMR AF: 0.0532

Gnomad ASJ AF: 0.0418

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00497

Gnomad FIN AF: 0.00612

Gnomad MID AF: 0.0605

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0684

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.112 AC: 17068 AN: 152110 Hom.: 2829 Cov.: 32 AF XY: 0.110 AC XY: 8143 AN XY: 74364

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.0531

Gnomad4 ASJ AF: 0.0418

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.00612

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0677

Alfa AF: 0.0321 Hom.: 579

Bravo AF: 0.127

Asia WGS AF: 0.0330 AC: 114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.24

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: rs17026635; hg19: chr1-216552367;