Variant 3-150927631-TACACACACACACACAC-TACACACACACACACACACAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_174878.3(CLRN1):c.*301_*304dupGTGT 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 0.0039 ( 8 hom., cov: 0)

Exomes 𝑓: 0.00055 ( 0 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:

ENSG00000260234 (HGNC:):

ENSG00000260234 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 3-150927631-T-TACAC is Benign according to our data. Variant chr3-150927631-T-TACAC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 343808.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Likely_benign=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00389 (579/148822) while in subpopulation AFR AF= 0.0132 (531/40336). AF 95% confidence interval is 0.0122. There are 8 homozygotes in gnomad4. There are 239 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLRN1	NM_174878.3 link	c.301_304dupGTGT		3_prime_UTR_variant	Exon 3 of 3	ENST00000327047.6	NP_777367.1	P58418-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLRN1	ENST00000327047 link	c.301_304dupGTGT		3_prime_UTR_variant	Exon 3 of 3	1	NM_174878.3	ENSP00000322280.1		P58418-3
ENSG00000260234	ENST00000569170.5 link	n.160+13947_160+13950dupGTGT		intron_variant	Intron 1 of 10	1		ENSP00000457784.1		H3BUT2

Frequencies

GnomAD3 genomes

AF:

0.00388

AC:

577

AN:

148710

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0132

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00181

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000429

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000119

Gnomad OTH

AF:

0.00497

GnomAD3 exomes

AF:

0.000953

AC:

AN:

99722

Hom.:

AF XY:

0.000719

AC XY:

AN XY:

54260

show subpopulations

Gnomad AFR exome

AF:

0.0163

Gnomad AMR exome

AF:

0.000263

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000482

Gnomad FIN exome

AF:

0.000240

Gnomad NFE exome

AF:

0.0000265

Gnomad OTH exome

AF:

0.000656

GnomAD4 exome

AF:

0.000548

AC:

178

AN:

324558

Hom.:

Cov.:

AF XY:

0.000397

AC XY:

AN XY:

181444

show subpopulations

Gnomad4 AFR exome

AF:

0.0129

Gnomad4 AMR exome

AF:

0.000489

Gnomad4 ASJ exome

AF:

0.0000811

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000334

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000564

Gnomad4 OTH exome

AF:

0.000605

GnomAD4 genome

AF:

0.00389

AC:

579

AN:

148822

Hom.:

Cov.:

AF XY:

0.00330

AC XY:

239

AN XY:

72456

show subpopulations

Gnomad4 AFR

AF:

0.0132

Gnomad4 AMR

AF:

0.00181

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000196

Gnomad4 SAS

AF:

0.000430

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000119

Gnomad4 OTH

AF:

0.00491

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

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Retinitis Pigmentosa, Dominant

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Aug 26, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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