Variant 3-150927631-T-TAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BA1

The NM_174878.3(CLRN1):c.*304_*305insGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.024 ( 80 hom., cov: 0)

Exomes 𝑓: 0.012 ( 2 hom. )

Consequence

CLRN1
NM_174878.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: -0.454

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:

(HGNC:):

links:

CLRN1-AS1 (HGNC:30895): (CLRN1 antisense RNA 1)

CLRN1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 3-150927631-T-TAC is Benign according to our data. Variant chr3-150927631-T-TAC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 343807.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0531 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLRN1	NM_174878.3 linkuse as main transcript	c.304_305insGT		3_prime_UTR_variant	3/3	ENST00000327047.6	NP_777367.1

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLRN1	ENST00000327047.6 linkuse as main transcript	c.304_305insGT	3_prime_UTR_variant	3/3	1	NM_174878.3	ENSP00000322280	P1	P58418-3
CLRN1	ENST00000295911.6 linkuse as main transcript	c.342+433_342+434insGT	intron_variant		1		ENSP00000295911		P58418-1
	ENST00000469268.1 linkuse as main transcript	n.235+36789_235+36790dup	intron_variant, non_coding_transcript_variant		4
CLRN1-AS1	ENST00000476886.5 linkuse as main transcript	n.123+75053_123+75054dup	intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0242

AC:

3600

AN:

148690

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0549

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00893

Gnomad ASJ

AF:

0.00965

Gnomad EAS

AF:

0.00508

Gnomad SAS

AF:

0.0167

Gnomad FIN

AF:

0.0504

Gnomad MID

AF:

0.0258

Gnomad NFE

AF:

0.00850

Gnomad OTH

AF:

0.0174

GnomAD3 exomes

AF:

0.0133

AC:

1325

AN:

99722

Hom.:

AF XY:

0.0133

AC XY:

722

AN XY:

54260

show subpopulations

Gnomad AFR exome

AF:

0.0558

Gnomad AMR exome

AF:

0.00726

Gnomad ASJ exome

AF:

0.00930

Gnomad EAS exome

AF:

0.00523

Gnomad SAS exome

AF:

0.0158

Gnomad FIN exome

AF:

0.0499

Gnomad NFE exome

AF:

0.00826

Gnomad OTH exome

AF:

0.0125

GnomAD4 exome

AF:

0.0119

AC:

3854

AN:

323720

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

2082

AN XY:

180926

show subpopulations

Gnomad4 AFR exome

AF:

0.0496

Gnomad4 AMR exome

AF:

0.00674

Gnomad4 ASJ exome

AF:

0.00821

Gnomad4 EAS exome

AF:

0.00560

Gnomad4 SAS exome

AF:

0.0143

Gnomad4 FIN exome

AF:

0.0474

Gnomad4 NFE exome

AF:

0.00775

Gnomad4 OTH exome

AF:

0.0132

GnomAD4 genome

AF:

0.0243

AC:

3614

AN:

148802

Hom.:

Cov.:

AF XY:

0.0260

AC XY:

1885

AN XY:

72438

show subpopulations

Gnomad4 AFR

AF:

0.0550

Gnomad4 AMR

AF:

0.00886

Gnomad4 ASJ

AF:

0.00965

Gnomad4 EAS

AF:

0.00509

Gnomad4 SAS

AF:

0.0168

Gnomad4 FIN

AF:

0.0504

Gnomad4 NFE

AF:

0.00852

Gnomad4 OTH

AF:

0.0196

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Retinitis pigmentosa-deafness syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Retinitis Pigmentosa, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 26, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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