rs9288125

Positions:

• chr2-152666597-A-C
• chr2-152666597-A-G
• chr2-152666597-A-T

Variant summary

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

The NM_001365597.4(PRPF40A):​c.1891-2345T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.793 in 152,016 control chromosomes in the GnomAD database, including 48,085 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 0.79 (48085 hom., cov: 31)
• Consequence: PRPF40A NM_001365597.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.547

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.829 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRPF40A	NM_001365597.4	c.1891-2345T>G		intron_variant		ENST00000545856.8	NP_001352526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRPF40A	ENST00000545856.8	c.1891-2345T>G		intron_variant		1	NM_001365597.4	ENSP00000444656	P3

Frequencies

GnomAD3 genomes AF: 0.793 AC: 120427 AN: 151898 Hom.: 48062 Cov.: 31

Gnomad AFR AF: 0.712

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.841

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.769

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.793 AC: 120501 AN: 152016 Hom.: 48085 Cov.: 31 AF XY: 0.794 AC XY: 59013 AN XY: 74328

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.841

Gnomad4 ASJ AF: 0.708

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.769

Gnomad4 FIN AF: 0.888

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.768

Alfa AF: 0.812 Hom.: 98273

Bravo AF: 0.787

Asia WGS AF: 0.745 AC: 2592 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.1
DANN	Benign	0.65

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: rs9288125; hg19: chr2-153523111;