dbSNP rs10497112: PRPF40A:c.211-435A>G (chr2-152716561-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_001365597.4(PRPF40A):c.211-435A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0323 in 152,296 control chromosomes in the GnomAD database, including 151 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 0.032 ( 151 hom., cov: 33)

Consequence

PRPF40A
NM_001365597.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0980

Publications

2 publications found

Variant links:

Genes affected

PRPF40A (HGNC:16463): (pre-mRNA processing factor 40 homolog A) Enables RNA binding activity. Involved in several processes, including cytoskeleton organization; regulation of cell shape; and regulation of cytokinesis. Located in nuclear matrix and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

PRPF40A links:

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new If you want to explore the variant's impact on the transcript NM_001365597.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.86).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0784 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365597.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRPF40A	NM_001365597.4	MANE Select	c.211-435A>G	intron	N/A	NP_001352526.1	F5H578
PRPF40A	NM_001395488.1		c.277-435A>G	intron	N/A	NP_001382417.1	A0A7N4I394
PRPF40A	NM_001365596.4		c.211-435A>G	intron	N/A	NP_001352525.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PRPF40A	ENST00000545856.8	TSL:1 MANE Select	c.211-435A>G	intron	N/A	ENSP00000444656.4	F5H578
PRPF40A	ENST00000493468.7	TSL:1	c.211-435A>G	intron	N/A	ENSP00000441656.2	H0YG38
PRPF40A	ENST00000410080.8	TSL:5	c.277-435A>G	intron	N/A	ENSP00000386458.4	A0A7N4I394

Frequencies

GnomAD3 genomes

AF:

0.0323

AC:

4916

AN:

152180

Hom.:

150

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0807

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00910

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0439

Gnomad MID

AF:

0.0411

Gnomad NFE

AF:

0.0128

Gnomad OTH

AF:

0.0229

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.0323

AC:

4925

AN:

152296

Hom.:

151

Cov.:

AF XY:

0.0327

AC XY:

2437

AN XY:

74478

show subpopulations

African (AFR)

AF:

0.0807

AC:

3353

AN:

41552

American (AMR)

AF:

0.00909

AC:

139

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00490

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00394

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0439

AC:

466

AN:

10614

Middle Eastern (MID)

AF:

0.0442

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0128

AC:

870

AN:

68028

Other (OTH)

AF:

0.0227

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

234

468

702

936

1170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0173

Hom.:

Bravo

AF:

0.0326

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

5.1

(source)

DANN

Benign

0.62

PhyloP100

-0.098

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over