Genetic Variant NM_174878.3:c.*1330T>C (chr3-150926606-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_174878.3(CLRN1):c.*1330T>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 0.00076 in 695,078 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00036 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00087 ( 7 hom. )

Consequence

CLRN1
NM_174878.3 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.778

Publications

0 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: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 3-150926606-A-G is Benign according to our data. Variant chr3-150926606-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 343796.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR,AD gene

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	UniProt
CLRN1	NM_174878.3	MANE Select	c.*1330T>C	3_prime_UTR	Exon 3 of 3	NP_777367.1	P58418-3
CLRN1	NM_001195794.1		c.*1330T>C	3_prime_UTR	Exon 4 of 4	NP_001182723.1	P58418-4
CLRN1	NM_001256819.2		c.*1643T>C	3_prime_UTR	Exon 4 of 4	NP_001243748.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CLRN1	ENST00000327047.6	TSL:1 MANE Select	c.*1330T>C	3_prime_UTR	Exon 3 of 3	ENSP00000322280.1	P58418-3
CLRN1	ENST00000295911.6	TSL:1	c.*246T>C	3_prime_UTR	Exon 4 of 4	ENSP00000295911.2	P58418-1
ENSG00000260234	ENST00000562308.5	TSL:1	n.103+14976T>C	intron	N/A	ENSP00000457487.1	H3BU62

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152248

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.00787

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00130

AC:

171

AN:

131802

AF XY:

0.00190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000366

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.00151

GnomAD4 exome

AF:

0.000872

AC:

473

AN:

542712

Hom.:

Cov.:

AF XY:

0.00128

AC XY:

372

AN XY:

291566

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

15278

American (AMR)

AF:

0.0000299

AC:

AN:

33418

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18776

East Asian (EAS)

AF:

0.0000968

AC:

AN:

30982

South Asian (SAS)

AF:

0.00712

AC:

429

AN:

60232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33440

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2320

European-Non Finnish (NFE)

AF:

0.0000125

AC:

AN:

318826

Other (OTH)

AF:

0.00122

AC:

AN:

29440

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

102

127

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:

0.000361

AC:

AN:

152366

Hom.:

Cov.:

AF XY:

0.000456

AC XY:

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41592

American (AMR)

AF:

0.000327

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00116

AC:

AN:

5194

South Asian (SAS)

AF:

0.00788

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68032

Other (OTH)

AF:

0.00284

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0000854

Hom.:

Bravo

AF:

0.0000945

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Usher syndrome type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.1

(source)

DANN

Benign

0.32

PhyloP100

0.78

Mutation Taster

=100/0

polymorphism

(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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over