3-150927631-TACACACACACACACAC-TACACACACACACAC

Variant names:

• chr3-150927631-TAC-T
• rs34027634
• NM_174878.3:c.*303_*304delGT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_174878.3(CLRN1):​c.*303_*304delGT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 462,398 control chromosomes in the GnomAD database, including 34,704 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.53 (21173 hom., cov: 0)
  • Exomes 𝑓: 0.44 (13531 hom.)
• Consequence: CLRN1 NM_174878.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0270
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 3-150927631-TAC-T is Benign according to our data. Variant chr3-150927631-TAC-T is described in ClinVar as Benign. ClinVar VariationId is 343809.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.569 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.*303_*304delGT		3_prime_UTR	Exon 3 of 3	NP_777367.1	P58418-3
	CLRN1	NM_001195794.1		c.*303_*304delGT		3_prime_UTR	Exon 4 of 4	NP_001182723.1	P58418-4
	CLRN1	NM_001256819.2		c.*616_*617delGT		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.*303_*304delGT		3_prime_UTR	Exon 3 of 3	ENSP00000322280.1	P58418-3
	CLRN1	ENST00000295911.6	TSL:1	c.342+432_342+433delGT		intron	N/A	ENSP00000295911.2	P58418-1
	ENSG00000260234	ENST00000562308.5	TSL:1	n.103+13949_103+13950delGT		intron	N/A	ENSP00000457487.1	H3BU62

Frequencies

GnomAD3 genomes AF: 0.535 AC: 79355 AN: 148458 Hom.: 21176 Cov.: 0

Gnomad AFR AF: 0.495

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.454

Gnomad EAS AF: 0.513

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.512

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.574

Gnomad OTH AF: 0.521

GnomAD2 exomes AF: 0.444 AC: 44311 AN: 99722 AF XY: 0.445

Gnomad AFR exome AF: 0.409

Gnomad AMR exome AF: 0.410

Gnomad ASJ exome AF: 0.427

Gnomad EAS exome AF: 0.429

Gnomad FIN exome AF: 0.432

Gnomad NFE exome AF: 0.480

Gnomad OTH exome AF: 0.456

GnomAD4 exome AF: 0.444 AC: 139490 AN: 313830 Hom.: 13531 AF XY: 0.443 AC XY: 77508 AN XY: 175136

African (AFR) AF: 0.417 AC: 3960 AN: 9492

American (AMR) AF: 0.403 AC: 10352 AN: 25666

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 4754 AN: 11794

East Asian (EAS) AF: 0.426 AC: 5510 AN: 12926

South Asian (SAS) AF: 0.412 AC: 21121 AN: 51282

European-Finnish (FIN) AF: 0.424 AC: 5661 AN: 13366

Middle Eastern (MID) AF: 0.425 AC: 555 AN: 1306

European-Non Finnish (NFE) AF: 0.467 AC: 80375 AN: 171950

Other (OTH) AF: 0.449 AC: 7202 AN: 16048

GnomAD4 genome AF: 0.534 AC: 79384 AN: 148568 Hom.: 21173 Cov.: 0 AF XY: 0.529 AC XY: 38259 AN XY: 72320

African (AFR) AF: 0.494 AC: 19900 AN: 40266

American (AMR) AF: 0.514 AC: 7643 AN: 14874

Ashkenazi Jewish (ASJ) AF: 0.454 AC: 1553 AN: 3420

East Asian (EAS) AF: 0.512 AC: 2613 AN: 5102

South Asian (SAS) AF: 0.495 AC: 2298 AN: 4644

European-Finnish (FIN) AF: 0.512 AC: 5152 AN: 10068

Middle Eastern (MID) AF: 0.490 AC: 141 AN: 288

European-Non Finnish (NFE) AF: 0.574 AC: 38451 AN: 66980

Other (OTH) AF: 0.521 AC: 1059 AN: 2034

Alfa AF: 0.418 Hom.: 963

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Retinitis pigmentosa-deafness syndrome (1)
-	-	1	Retinitis Pigmentosa, Dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.027
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: rs34027634; hg19: chr3-150645418; COSMIC: COSV55804470; COSMIC: COSV55804470;