rs16846663

Variant names:

• chr3-150940477-G-A
• rs16846663
• NM_174878.3:c.433+1105C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-150940477-G-A
• chr3-150940477-G-C

Variant summary

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

The NM_001195794.1(CLRN1):​c.472+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0185 in 1,534,678 control chromosomes in the GnomAD database, including 2,490 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (330 hom., cov: 32)
  • Exomes 𝑓: 0.017 (2160 hom.)
• Consequence: CLRN1 NM_001195794.1 splice_region, intron
• Scores: Splicing: ADA: 0.004845
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.452
• 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=-0.83).
• BP6: Variant 3-150940477-G-A is Benign according to our data. Variant chr3-150940477-G-A is described in ClinVar as Benign. ClinVar VariationId is 226524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.304 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001195794.1. 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.433+1105C>T		intron	N/A	NP_777367.1	P58418-3
	CLRN1	NM_001195794.1		c.472+4C>T		splice_region intron	N/A	NP_001182723.1	P58418-4
	CLRN1	NM_001256819.2		c.*47+1105C>T		intron	N/A	NP_001243748.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLRN1	ENST00000327047.6	TSL:1 MANE Select	c.433+1105C>T		intron	N/A	ENSP00000322280.1	P58418-3
	CLRN1	ENST00000328863.8	TSL:1	c.472+4C>T		splice_region intron	N/A	ENSP00000329158.4	P58418-4
	CLRN1	ENST00000295911.6	TSL:1	c.205+1105C>T		intron	N/A	ENSP00000295911.2	P58418-1

Frequencies

GnomAD3 genomes AF: 0.0319 AC: 4854 AN: 152172 Hom.: 330 Cov.: 32

Gnomad AFR AF: 0.0370

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.0413

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.0603

Gnomad FIN AF: 0.0343

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00459

Gnomad OTH AF: 0.0244

GnomAD2 exomes AF: 0.0492 AC: 6602 AN: 134086 AF XY: 0.0452

Gnomad AFR exome AF: 0.0405

Gnomad AMR exome AF: 0.0630

Gnomad ASJ exome AF: 0.00314

Gnomad EAS exome AF: 0.323

Gnomad FIN exome AF: 0.0347

Gnomad NFE exome AF: 0.00383

Gnomad OTH exome AF: 0.0347

GnomAD4 exome AF: 0.0171 AC: 23576 AN: 1382388 Hom.: 2160 Cov.: 30 AF XY: 0.0174 AC XY: 11847 AN XY: 682154

African (AFR) AF: 0.0365 AC: 1152 AN: 31550

American (AMR) AF: 0.0595 AC: 2122 AN: 35670

Ashkenazi Jewish (ASJ) AF: 0.00326 AC: 82 AN: 25130

East Asian (EAS) AF: 0.310 AC: 11048 AN: 35670

South Asian (SAS) AF: 0.0405 AC: 3198 AN: 79034

European-Finnish (FIN) AF: 0.0339 AC: 1147 AN: 33866

Middle Eastern (MID) AF: 0.0160 AC: 91 AN: 5690

European-Non Finnish (NFE) AF: 0.00256 AC: 2757 AN: 1077948

Other (OTH) AF: 0.0342 AC: 1979 AN: 57830

GnomAD4 genome AF: 0.0319 AC: 4859 AN: 152290 Hom.: 330 Cov.: 32 AF XY: 0.0355 AC XY: 2646 AN XY: 74450

African (AFR) AF: 0.0370 AC: 1537 AN: 41566

American (AMR) AF: 0.0413 AC: 632 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00259 AC: 9 AN: 3472

East Asian (EAS) AF: 0.317 AC: 1636 AN: 5162

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4824

European-Finnish (FIN) AF: 0.0343 AC: 364 AN: 10614

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00459 AC: 312 AN: 68036

Other (OTH) AF: 0.0279 AC: 59 AN: 2112

Alfa AF: 0.0198 Hom.: 467

Bravo AF: 0.0345

Asia WGS AF: 0.182 AC: 632 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.40
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0048
dbscSNV1_RF	Benign	0.070
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: rs16846663; hg19: chr3-150658264; COSMIC: COSV107329680; COSMIC: COSV107329680;