rs11205362

Variant names:

• chr1-150325734-G-A
• rs11205362
• NM_004698.4:c.146-17G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-150325734-G-A
• chr1-150325734-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_004698.4(PRPF3):​c.146-17G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,609,420 control chromosomes in the GnomAD database, including 9,760 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.082 (678 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9082 hom.)
• Consequence: PRPF3 NM_004698.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.404
• Publications: 16 publications found

Genes affected

PRPF3 (HGNC:17348): (pre-mRNA processing factor 3) The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. This gene product is one of several proteins that associate with U4 and U6 snRNPs. Mutations in this gene are associated with retinitis pigmentosa-18. [provided by RefSeq, Jul 2008]

PRPF3 Gene-Disease associations (from GenCC):

• retinitis pigmentosa 18

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• retinitis pigmentosa

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 1-150325734-G-A is Benign according to our data. Variant chr1-150325734-G-A is described in ClinVar as Benign. ClinVar VariationId is 1165123.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PRPF3	NM_004698.4	c.146-17G>A		intron_variant	Intron 2 of 15	ENST00000324862.7	NP_004689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF3	ENST00000324862.7	c.146-17G>A		intron_variant	Intron 2 of 15	1	NM_004698.4	ENSP00000315379.6
PRPF3	ENST00000496202.5	n.308-17G>A		intron_variant	Intron 2 of 7	1

Frequencies

GnomAD3 genomes AF: 0.0819 AC: 12449 AN: 151974 Hom.: 678 Cov.: 32

Gnomad AFR AF: 0.0208

Gnomad AMI AF: 0.0703

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0963

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0288

Gnomad FIN AF: 0.155

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.0675

GnomAD2 exomes AF: 0.0839 AC: 21101 AN: 251456 AF XY: 0.0842

Gnomad AFR exome AF: 0.0183

Gnomad AMR exome AF: 0.0454

Gnomad ASJ exome AF: 0.0922

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.153

Gnomad NFE exome AF: 0.118

Gnomad OTH exome AF: 0.0963

GnomAD4 exome AF: 0.106 AC: 154364 AN: 1457328 Hom.: 9082 Cov.: 32 AF XY: 0.104 AC XY: 75563 AN XY: 725126

African (AFR) AF: 0.0175 AC: 582 AN: 33334

American (AMR) AF: 0.0478 AC: 2133 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.0976 AC: 2531 AN: 25936

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39536

South Asian (SAS) AF: 0.0327 AC: 2810 AN: 85980

European-Finnish (FIN) AF: 0.144 AC: 7638 AN: 53160

Middle Eastern (MID) AF: 0.0745 AC: 422 AN: 5662

European-Non Finnish (NFE) AF: 0.119 AC: 132299 AN: 1109074

Other (OTH) AF: 0.0990 AC: 5947 AN: 60042

GnomAD4 genome AF: 0.0818 AC: 12445 AN: 152092 Hom.: 678 Cov.: 32 AF XY: 0.0810 AC XY: 6026 AN XY: 74356

African (AFR) AF: 0.0207 AC: 859 AN: 41492

American (AMR) AF: 0.0675 AC: 1030 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0963 AC: 334 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0293 AC: 141 AN: 4816

European-Finnish (FIN) AF: 0.155 AC: 1638 AN: 10570

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8216 AN: 67992

Other (OTH) AF: 0.0668 AC: 141 AN: 2110

Alfa AF: 0.105 Hom.: 1005

Bravo AF: 0.0726

Asia WGS AF: 0.0180 AC: 66 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	11
DANN	Benign	0.53
PhyloP100		-0.40
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: rs11205362; hg19: chr1-150298192;