rs9288134

chr2-152716849-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365597.4(PRPF40A):c.210+381C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.059 in 152,046 control chromosomes in the GnomAD database, including 807 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 0.059 (807 hom., cov: 33)
• Consequence: PRPF40A NM_001365597.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.544

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PRPF40A	NM_001365597.4	c.210+381C>G		intron_variant		ENST00000545856.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PRPF40A	ENST00000545856.8	c.210+381C>G		intron_variant		1	NM_001365597.4	P3

Frequencies

GnomAD3 genomes AF: 0.0588 AC: 8937 AN: 151928 Hom.: 805 Cov.: 33

Gnomad AFR AF: 0.194

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0305

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.00705

Gnomad FIN AF: 0.000473

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00441

Gnomad OTH AF: 0.0498

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

GnomAD4 genome AF: 0.0590 AC: 8966 AN: 152046 Hom.: 807 Cov.: 33 AF XY: 0.0568 AC XY: 4219 AN XY: 74336

Gnomad4 AFR AF: 0.194

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.00706

Gnomad4 FIN AF: 0.000473

Gnomad4 NFE AF: 0.00441

Gnomad4 OTH AF: 0.0502

Alfa AF: 0.0349 Hom.: 53

Bravo AF: 0.0678

Asia WGS AF: 0.0200 AC: 71 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.5
Dann	Benign	0.37

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

Publications

LitVar

Other links and lift over

dbSNP: rs9288134; hg19: chr2-153573363;