rs301760

chr1-216164191-G-Achr1-216164191-G-T

Variant summary

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

The NM_206933.4(USH2A):c.4627+11061C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.61 in 151,864 control chromosomes in the GnomAD database, including 28,579 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 0.61 (28579 hom., cov: 32)
• Consequence: USH2A NM_206933.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4	c.4627+11061C>T		intron_variant		ENST00000307340.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8	c.4627+11061C>T		intron_variant		1	NM_206933.4	P1
USH2A	ENST00000674083.1	c.4627+11061C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.610 AC: 92536 AN: 151746 Hom.: 28567 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.613

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.782

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.612

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

GnomAD4 genome AF: 0.610 AC: 92578 AN: 151864 Hom.: 28579 Cov.: 32 AF XY: 0.616 AC XY: 45686 AN XY: 74194

Gnomad4 AFR AF: 0.511

Gnomad4 AMR AF: 0.614

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.696

Gnomad4 FIN AF: 0.726

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.613

Alfa AF: 0.556 Hom.: 3253

Bravo AF: 0.596

Asia WGS AF: 0.717 AC: 2497 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	0.15
Dann	Benign	0.68

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: rs301760; hg19: chr1-216337533; COSMIC: COSV56346063;