dbSNP rs4330896: USH2A:c.11712-3147C>T (chr1-215731531-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_206933.4(USH2A):c.11712-3147C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.68 in 152,030 control chromosomes in the GnomAD database, including 36,206 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 0.68 ( 36206 hom., cov: 32)

Consequence

USH2A
NM_206933.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.46

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

Usher syndrome type 2A
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
Usher syndrome type 2
Inheritance: Unknown, AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
retinitis pigmentosa 39
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

USH2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.778 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206933.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	NM_206933.4	MANE Select	c.11712-3147C>T		intron	N/A	NP_996816.3	O75445-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	USH2A	ENST00000307340.8	TSL:1 MANE Select	c.11712-3147C>T		intron	N/A	ENSP00000305941.3	O75445-1
	USH2A	ENST00000674083.1		c.11712-3147C>T		intron	N/A	ENSP00000501296.1	O75445-3

Frequencies

GnomAD3 genomes

AF:

0.680

AC:

103323

AN:

151912

Hom.:

36195

Cov.:

show subpopulations

Gnomad AFR

AF:

0.507

Gnomad AMI

AF:

0.735

Gnomad AMR

AF:

0.671

Gnomad ASJ

AF:

0.732

Gnomad EAS

AF:

0.598

Gnomad SAS

AF:

0.691

Gnomad FIN

AF:

0.716

Gnomad MID

AF:

0.766

Gnomad NFE

AF:

0.783

Gnomad OTH

AF:

0.697

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

GnomAD4 genome

AF:

0.680

AC:

103352

AN:

152030

Hom.:

36206

Cov.:

AF XY:

0.675

AC XY:

50177

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.506

AC:

20963

AN:

41442

American (AMR)

AF:

0.670

AC:

10225

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.732

AC:

2539

AN:

3468

East Asian (EAS)

AF:

0.599

AC:

3091

AN:

5158

South Asian (SAS)

AF:

0.692

AC:

3334

AN:

4818

European-Finnish (FIN)

AF:

0.716

AC:

7586

AN:

10588

Middle Eastern (MID)

AF:

0.769

AC:

226

AN:

294

European-Non Finnish (NFE)

AF:

0.783

AC:

53251

AN:

67982

Other (OTH)

AF:

0.696

AC:

1468

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1605

3210

4814

6419

8024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

810

1620

2430

3240

4050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.757

Hom.:

25571

Bravo

AF:

0.666

Asia WGS

AF:

0.608

AC:

2114

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.16

(source)

DANN

Benign

0.26

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over