chr2-152716894-C-G

Variant names:

• chr2-152716894-C-G
• rs4664604
• NM_001365597.4:c.210+336G>C

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+336G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.79 in 152,050 control chromosomes in the GnomAD database, including 47,925 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 (47925 hom., cov: 30)
• Consequence: PRPF40A NM_001365597.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.680
• Publications: 4 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.835 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF40A	NM_001365597.4	MANE Select	c.210+336G>C		intron	N/A	NP_001352526.1
	PRPF40A	NM_001395488.1		c.276+462G>C		intron	N/A	NP_001382417.1
	PRPF40A	NM_001365596.4		c.210+336G>C		intron	N/A	NP_001352525.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRPF40A	ENST00000545856.8	TSL:1 MANE Select	c.210+336G>C		intron	N/A	ENSP00000444656.4
	PRPF40A	ENST00000493468.7	TSL:1	c.210+336G>C		intron	N/A	ENSP00000441656.2
	PRPF40A	ENST00000410080.8	TSL:5	c.276+462G>C		intron	N/A	ENSP00000386458.4

Frequencies

GnomAD3 genomes AF: 0.791 AC: 120113 AN: 151930 Hom.: 47902 Cov.: 30

Gnomad AFR AF: 0.697

Gnomad AMI AF: 0.833

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.708

Gnomad EAS AF: 0.734

Gnomad SAS AF: 0.767

Gnomad FIN AF: 0.888

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.830

Gnomad OTH AF: 0.775

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

GnomAD4 genome AF: 0.790 AC: 120185 AN: 152050 Hom.: 47925 Cov.: 30 AF XY: 0.792 AC XY: 58852 AN XY: 74336

African (AFR) AF: 0.697 AC: 28862 AN: 41422

American (AMR) AF: 0.848 AC: 12965 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.708 AC: 2459 AN: 3472

East Asian (EAS) AF: 0.733 AC: 3778 AN: 5154

South Asian (SAS) AF: 0.767 AC: 3689 AN: 4808

European-Finnish (FIN) AF: 0.888 AC: 9403 AN: 10588

Middle Eastern (MID) AF: 0.714 AC: 210 AN: 294

European-Non Finnish (NFE) AF: 0.830 AC: 56436 AN: 67992

Other (OTH) AF: 0.769 AC: 1625 AN: 2114

Alfa AF: 0.786 Hom.: 2826

Bravo AF: 0.785

Asia WGS AF: 0.746 AC: 2595 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	4.2
DANN	Benign	0.71
PhyloP100		-0.68
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: rs4664604; hg19: chr2-153573408;