NM_174878.3:c.*315C>T

Variant names:

• chr3-150927621-G-A
• rs1456138
• NM_174878.3:c.*315C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_174878.3(CLRN1):​c.*315C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 514,546 control chromosomes in the GnomAD database, including 131,785 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.76 (44699 hom., cov: 29)
  • Exomes 𝑓: 0.69 (87086 hom.)
• Consequence: CLRN1 NM_174878.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0100
• Publications: 8 publications found

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]

ENSG00000260234 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 3-150927621-G-A is Benign according to our data. Variant chr3-150927621-G-A is described in ClinVar as Benign. ClinVar VariationId is 343805.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.915 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN1	NM_174878.3	MANE Select	c.*315C>T		3_prime_UTR	Exon 3 of 3	NP_777367.1	P58418-3
	CLRN1	NM_001195794.1		c.*315C>T		3_prime_UTR	Exon 4 of 4	NP_001182723.1	P58418-4
	CLRN1	NM_001256819.2		c.*628C>T		3_prime_UTR	Exon 4 of 4	NP_001243748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN1	ENST00000327047.6	TSL:1 MANE Select	c.*315C>T		3_prime_UTR	Exon 3 of 3	ENSP00000322280.1	P58418-3
	CLRN1	ENST00000295911.6	TSL:1	c.342+444C>T		intron	N/A	ENSP00000295911.2	P58418-1
	ENSG00000260234	ENST00000562308.5	TSL:1	n.103+13961C>T		intron	N/A	ENSP00000457487.1	H3BU62

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115213 AN: 151544 Hom.: 44659 Cov.: 29

Gnomad AFR AF: 0.923

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.706

Gnomad ASJ AF: 0.553

Gnomad EAS AF: 0.805

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.636

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.729

GnomAD2 exomes AF: 0.692 AC: 89543 AN: 129488 AF XY: 0.685

Gnomad AFR exome AF: 0.932

Gnomad AMR exome AF: 0.658

Gnomad ASJ exome AF: 0.565

Gnomad EAS exome AF: 0.808

Gnomad FIN exome AF: 0.679

Gnomad NFE exome AF: 0.712

Gnomad OTH exome AF: 0.696

GnomAD4 exome AF: 0.687 AC: 249403 AN: 362884 Hom.: 87086 Cov.: 1 AF XY: 0.679 AC XY: 137380 AN XY: 202400

African (AFR) AF: 0.923 AC: 10161 AN: 11008

American (AMR) AF: 0.661 AC: 19261 AN: 29132

Ashkenazi Jewish (ASJ) AF: 0.561 AC: 7592 AN: 13534

East Asian (EAS) AF: 0.799 AC: 11647 AN: 14580

South Asian (SAS) AF: 0.605 AC: 35976 AN: 59490

European-Finnish (FIN) AF: 0.666 AC: 10092 AN: 15142

Middle Eastern (MID) AF: 0.651 AC: 991 AN: 1522

European-Non Finnish (NFE) AF: 0.704 AC: 140719 AN: 200002

Other (OTH) AF: 0.702 AC: 12964 AN: 18474

GnomAD4 genome AF: 0.760 AC: 115310 AN: 151662 Hom.: 44699 Cov.: 29 AF XY: 0.757 AC XY: 56063 AN XY: 74058

African (AFR) AF: 0.923 AC: 38185 AN: 41362

American (AMR) AF: 0.706 AC: 10742 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.553 AC: 1914 AN: 3464

East Asian (EAS) AF: 0.804 AC: 4151 AN: 5160

South Asian (SAS) AF: 0.628 AC: 3008 AN: 4786

European-Finnish (FIN) AF: 0.677 AC: 7079 AN: 10464

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.704 AC: 47809 AN: 67892

Other (OTH) AF: 0.733 AC: 1544 AN: 2106

Alfa AF: 0.708 Hom.: 4619

Bravo AF: 0.772

Asia WGS AF: 0.750 AC: 2605 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Usher syndrome type 3 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.90
DANN	Benign	0.57
PhyloP100		0.010
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1456138; hg19: chr3-150645408;