Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_174878.3(CLRN1):c.433+1106T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00019 in 1,534,898 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 1 hom. )

Consequence

CLRN1
NM_174878.3 intron

Scores

Splicing: ADA: 0.00008991

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.275

Publications

2 publications found

Variant links:

Genes affected

CLRN1 (HGNC:12605): (clarin 1) This gene encodes a protein that contains a cytosolic N-terminus, multiple helical transmembrane domains, and an endoplasmic reticulum membrane retention signal, TKGH, in the C-terminus. The encoded protein may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIIa. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

CLRN1 links:

ENSG00000260234 (HGNC:):

ENSG00000260234 links:

SIAH2-AS1 (HGNC:40526): (SIAH2 antisense RNA 1)

SIAH2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 3-150940476-A-G is Benign according to our data. Variant chr3-150940476-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 228522.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_174878.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLRN1	NM_174878.3	MANE Select	c.433+1106T>C	intron	N/A	NP_777367.1
CLRN1	NM_001195794.1		c.472+5T>C	splice_region intron	N/A	NP_001182723.1
CLRN1	NM_001256819.2		c.*47+1106T>C	intron	N/A	NP_001243748.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CLRN1	ENST00000327047.6	TSL:1 MANE Select	c.433+1106T>C	intron	N/A	ENSP00000322280.1
CLRN1	ENST00000328863.8	TSL:1	c.472+5T>C	splice_region intron	N/A	ENSP00000329158.4
CLRN1	ENST00000295911.6	TSL:1	c.205+1106T>C	intron	N/A	ENSP00000295911.2

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.000462

AC:

AN:

134118

AF XY:

0.000534

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000165

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00410

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000114

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.000184

AC:

255

AN:

1382538

Hom.:

Cov.:

AF XY:

0.000217

AC XY:

148

AN XY:

682236

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31556

American (AMR)

AF:

0.000112

AC:

AN:

35668

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25142

East Asian (EAS)

AF:

0.00330

AC:

118

AN:

35708

South Asian (SAS)

AF:

0.000417

AC:

AN:

79060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33878

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5692

European-Non Finnish (NFE)

AF:

0.0000770

AC:

AN:

1077996

Other (OTH)

AF:

0.000277

AC:

AN:

57838

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000243

AC:

AN:

152360

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41584

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00424

AC:

AN:

5186

South Asian (SAS)

AF:

0.000622

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68040

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.0000530

Hom.:

Bravo

AF:

0.000204

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CLRN1-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

3.1

(source)

DANN

Benign

0.39

PhyloP100

0.28

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000090

dbscSNV1_RF

Benign

0.0

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.

NM_174878.3:c.433+1106T>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over