rs301760

Variant names:

• chr1-216164191-G-A
• rs301760
• NM_206933.4:c.4627+11061C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-216164191-G-A
• chr1-216164191-G-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• Usher syndrome type 2

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Usher syndrome type 2A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa 39

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
USH2A	NM_206933.4	c.4627+11061C>T		intron_variant	Intron 21 of 71	ENST00000307340.8	NP_996816.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
USH2A	ENST00000307340.8	c.4627+11061C>T		intron_variant	Intron 21 of 71	1	NM_206933.4	ENSP00000305941.3
USH2A	ENST00000674083.1	c.4627+11061C>T		intron_variant	Intron 21 of 72			ENSP00000501296.1

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

African (AFR) AF: 0.511 AC: 21145 AN: 41412

American (AMR) AF: 0.614 AC: 9351 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 2122 AN: 3470

East Asian (EAS) AF: 0.781 AC: 4022 AN: 5148

South Asian (SAS) AF: 0.696 AC: 3359 AN: 4828

European-Finnish (FIN) AF: 0.726 AC: 7662 AN: 10552

Middle Eastern (MID) AF: 0.575 AC: 168 AN: 292

European-Non Finnish (NFE) AF: 0.629 AC: 42731 AN: 67916

Other (OTH) AF: 0.613 AC: 1289 AN: 2104

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
PhyloP100		-1.3
Mutation Taster		=100/0	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: rs301760; hg19: chr1-216337533; COSMIC: COSV56346063;