rs113817098

Variant names:

• chr3-150926745-A-G
• rs113817098
• NM_174878.3:c.*1191T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_174878.3(CLRN1):​c.*1191T>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 0.000718 in 1,582,786 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00041 (6 hom.)
• Consequence: CLRN1 NM_174878.3 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.55
• Publications: 0 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=-0.88).
• BP6: Variant 3-150926745-A-G is Benign according to our data. Variant chr3-150926745-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 900992.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00363 (553/152308) while in subpopulation AFR AF = 0.0128 (534/41572). AF 95% confidence interval is 0.0119. There are 5 homozygotes in GnomAd4. There are 256 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN1	NM_174878.3	MANE Select	c.*1191T>C		3_prime_UTR	Exon 3 of 3	NP_777367.1	P58418-3
	CLRN1	NM_001195794.1		c.*1191T>C		3_prime_UTR	Exon 4 of 4	NP_001182723.1	P58418-4
	CLRN1	NM_001256819.2		c.*1504T>C		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.*1191T>C		3_prime_UTR	Exon 3 of 3	ENSP00000322280.1	P58418-3
	CLRN1	ENST00000295911.6	TSL:1	c.*107T>C		3_prime_UTR	Exon 4 of 4	ENSP00000295911.2	P58418-1
	ENSG00000260234	ENST00000562308.5	TSL:1	n.103+14837T>C		intron	N/A	ENSP00000457487.1	H3BU62

Frequencies

GnomAD3 genomes AF: 0.00360 AC: 548 AN: 152190 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000916

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00107 AC: 269 AN: 250838 AF XY: 0.000715

Gnomad AFR exome AF: 0.0148

Gnomad AMR exome AF: 0.000695

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000654

GnomAD4 exome AF: 0.000408 AC: 583 AN: 1430478 Hom.: 6 Cov.: 27 AF XY: 0.000356 AC XY: 254 AN XY: 713654

African (AFR) AF: 0.0143 AC: 472 AN: 32902

American (AMR) AF: 0.000806 AC: 36 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25938

East Asian (EAS) AF: 0.00 AC: 0 AN: 39548

South Asian (SAS) AF: 0.0000701 AC: 6 AN: 85566

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.000209 AC: 1 AN: 4794

European-Non Finnish (NFE) AF: 0.00000646 AC: 7 AN: 1084376

Other (OTH) AF: 0.00103 AC: 61 AN: 59308

GnomAD4 genome AF: 0.00363 AC: 553 AN: 152308 Hom.: 5 Cov.: 32 AF XY: 0.00344 AC XY: 256 AN XY: 74476

African (AFR) AF: 0.0128 AC: 534 AN: 41572

American (AMR) AF: 0.000915 AC: 14 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68022

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

Alfa AF: 0.00249 Hom.: 1

Bravo AF: 0.00432

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.077
DANN	Benign	0.66
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism

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: rs113817098; hg19: chr3-150644532;