rs9288134

Variant names:

• chr2-152716849-G-C
• rs9288134
• NM_001365597.4:c.210+381C>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF40A	NM_001365597.4	MANE Select	c.210+381C>G		intron	N/A	NP_001352526.1	F5H578
	PRPF40A	NM_001395488.1		c.276+507C>G		intron	N/A	NP_001382417.1	A0A7N4I394
	PRPF40A	NM_001365596.4		c.210+381C>G		intron	N/A	NP_001352525.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF40A	ENST00000545856.8	TSL:1 MANE Select	c.210+381C>G		intron	N/A	ENSP00000444656.4	F5H578
	PRPF40A	ENST00000493468.7	TSL:1	c.210+381C>G		intron	N/A	ENSP00000441656.2	H0YG38
	PRPF40A	ENST00000410080.8	TSL:5	c.276+507C>G		intron	N/A	ENSP00000386458.4	A0A7N4I394

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

African (AFR) AF: 0.194 AC: 8024 AN: 41410

American (AMR) AF: 0.0304 AC: 464 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.000580 AC: 3 AN: 5176

South Asian (SAS) AF: 0.00706 AC: 34 AN: 4818

European-Finnish (FIN) AF: 0.000473 AC: 5 AN: 10574

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00441 AC: 300 AN: 67998

Other (OTH) AF: 0.0502 AC: 106 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.37
PhyloP100		-0.54
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9288134; hg19: chr2-153573363;