Variant chr1-215625732-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_206933.4(USH2A):c.*49A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 1,549,140 control chromosomes in the GnomAD database, including 706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 203 hom., cov: 32)

Exomes 𝑓: 0.013 ( 503 hom. )

Consequence

USH2A
NM_206933.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.148

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-215625732-T-G is Benign according to our data. Variant chr1-215625732-T-G is described in ClinVar as [Benign]. Clinvar id is 1227419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-215625732-T-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0912 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
USH2A	NM_206933.4 linkuse as main transcript	c.*49A>C		3_prime_UTR_variant	72/72	ENST00000307340.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
USH2A	ENST00000307340.8 linkuse as main transcript	c.*49A>C		3_prime_UTR_variant	72/72	1	NM_206933.4	P1	O75445-1
USH2A	ENST00000674083.1 linkuse as main transcript	c.*49A>C		3_prime_UTR_variant	73/73				O75445-3

Frequencies

GnomAD3 genomes

AF:

0.0330

AC:

5022

AN:

152106

Hom.:

200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0935

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0179

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.0287

Gnomad SAS

AF:

0.0707

Gnomad FIN

AF:

0.00433

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00409

Gnomad OTH

AF:

0.0268

GnomAD3 exomes

AF:

0.0199

AC:

4983

AN:

250738

Hom.:

166

AF XY:

0.0209

AC XY:

2829

AN XY:

135518

show subpopulations

Gnomad AFR exome

AF:

0.0926

Gnomad AMR exome

AF:

0.00786

Gnomad ASJ exome

AF:

0.00209

Gnomad EAS exome

AF:

0.0187

Gnomad SAS exome

AF:

0.0712

Gnomad FIN exome

AF:

0.00301

Gnomad NFE exome

AF:

0.00461

Gnomad OTH exome

AF:

0.0133

GnomAD4 exome

AF:

0.0126

AC:

17660

AN:

1396916

Hom.:

503

Cov.:

AF XY:

0.0140

AC XY:

9759

AN XY:

698764

show subpopulations

Gnomad4 AFR exome

AF:

0.0958

Gnomad4 AMR exome

AF:

0.00870

Gnomad4 ASJ exome

AF:

0.00229

Gnomad4 EAS exome

AF:

0.0494

Gnomad4 SAS exome

AF:

0.0678

Gnomad4 FIN exome

AF:

0.00251

Gnomad4 NFE exome

AF:

0.00498

Gnomad4 OTH exome

AF:

0.0168

GnomAD4 genome

AF:

0.0331

AC:

5041

AN:

152224

Hom.:

203

Cov.:

AF XY:

0.0325

AC XY:

2418

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.0937

Gnomad4 AMR

AF:

0.0179

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.0290

Gnomad4 SAS

AF:

0.0710

Gnomad4 FIN

AF:

0.00433

Gnomad4 NFE

AF:

0.00409

Gnomad4 OTH

AF:

0.0265

Alfa

AF:

0.00991

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.0570

AC:

199

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.37

DANN

Benign

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over