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:

Genome browser will be placed here

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PRPF31	NM_015629.4 link	c.-9+14G>A	intron_variant	Intron 1 of 13	ENST00000321030.9	NP_056444.3	Q8WWY3-1
PRPF31	XM_006723137.5 link	c.-39+14G>A	intron_variant	Intron 1 of 13		XP_006723200.1	Q8WWY3-1
PRPF31	XM_047438587.1 link	c.-9+14G>A	intron_variant	Intron 1 of 9		XP_047294543.1
TFPT	NM_013342.4 link	c.-542C>T	upstream_gene_variant		ENST00000391759.6	NP_037474.1	P0C1Z6-1A0A024R4Q5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PRPF31	ENST00000321030.9 link	c.-9+14G>A		intron_variant	Intron 1 of 13	1	NM_015629.4	ENSP00000324122.4		Q8WWY3-1
TFPT	ENST00000391759.6 link	c.-542C>T		upstream_gene_variant		1	NM_013342.4	ENSP00000375639.1		P0C1Z6-1

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 v4.3

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over