dbSNP rs4806711: PRPF31:c.-9+14G>A (chr19-54115811-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_015629.4(PRPF31):c.-9+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.817 in 219,942 control chromosomes in the GnomAD database, including 73,513 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.82 ( 51693 hom., cov: 33)

Exomes 𝑓: 0.80 ( 21820 hom. )

Consequence

PRPF31
NM_015629.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

19 publications found

Variant links:

Genes affected

PRPF31 (HGNC:15446): (pre-mRNA processing factor 31) This gene encodes a component of the spliceosome complex and is one of several retinitis pigmentosa-causing genes. When the gene product is added to the spliceosome complex, activation occurs.[provided by RefSeq, Jan 2009]

PRPF31 links:

TFPT (HGNC:13630): (TCF3 fusion partner) Predicted to enable DNA binding activity and protein kinase binding activity. Involved in apoptotic signaling pathway. Located in nucleoplasm. Part of Ino80 complex. [provided by Alliance of Genome Resources, Apr 2022]

TFPT links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.877 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015629.4. 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
	PRPF31	NM_015629.4	MANE Select	c.-9+14G>A		intron	N/A	NP_056444.3
	TFPT	NM_013342.4	MANE Select	c.-542C>T		upstream_gene	N/A	NP_037474.1	P0C1Z6-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRPF31	ENST00000321030.9	TSL:1 MANE Select	c.-9+14G>A	intron	N/A	ENSP00000324122.4	Q8WWY3-1
PRPF31	ENST00000447810.5	TSL:5	c.-70G>A	5_prime_UTR	Exon 1 of 8	ENSP00000395089.1	E7EU94
PRPF31	ENST00000951323.1		c.-9+14G>A	intron	N/A	ENSP00000621382.1

Frequencies

GnomAD3 genomes

AF:

0.823

AC:

125155

AN:

152070

Hom.:

51637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.885

Gnomad AMI

AF:

0.718

Gnomad AMR

AF:

0.803

Gnomad ASJ

AF:

0.783

Gnomad EAS

AF:

0.822

Gnomad SAS

AF:

0.795

Gnomad FIN

AF:

0.779

Gnomad MID

AF:

0.769

Gnomad NFE

AF:

0.803

Gnomad OTH

AF:

0.821

GnomAD4 exome

AF:

0.802

AC:

54317

AN:

67754

Hom.:

21820

Cov.:

AF XY:

0.802

AC XY:

25751

AN XY:

32098

show subpopulations

African (AFR)

AF:

0.886

AC:

2572

AN:

2904

American (AMR)

AF:

0.769

AC:

1697

AN:

2206

Ashkenazi Jewish (ASJ)

AF:

0.772

AC:

3113

AN:

4030

East Asian (EAS)

AF:

0.772

AC:

6928

AN:

8972

South Asian (SAS)

AF:

0.793

AC:

1607

AN:

2026

European-Finnish (FIN)

AF:

0.753

AC:

223

AN:

296

Middle Eastern (MID)

AF:

0.755

AC:

293

AN:

388

European-Non Finnish (NFE)

AF:

0.807

AC:

33534

AN:

41552

Other (OTH)

AF:

0.809

AC:

4350

AN:

5380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

550

1101

1651

2202

2752

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.823

AC:

125269

AN:

152188

Hom.:

51693

Cov.:

AF XY:

0.819

AC XY:

60923

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.885

AC:

36732

AN:

41514

American (AMR)

AF:

0.803

AC:

12275

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.783

AC:

2718

AN:

3472

East Asian (EAS)

AF:

0.821

AC:

4251

AN:

5176

South Asian (SAS)

AF:

0.795

AC:

3836

AN:

4826

European-Finnish (FIN)

AF:

0.779

AC:

8249

AN:

10594

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.803

AC:

54585

AN:

68006

Other (OTH)

AF:

0.823

AC:

1739

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1155

2310

3466

4621

5776

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

884

1768

2652

3536

4420

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.808

Hom.:

38622

Bravo

AF:

0.824

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.51

(source)

PhyloP100

-1.6

PromoterAI

0.0028

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over