chr3-150004607-T-G

Position:

• chr3-150004607-T-G

Variant summary

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

The ENST00000494827.5(PFN2):​c.-16+18013A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,918 control chromosomes in the GnomAD database, including 7,460 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 0.31 (7460 hom., cov: 31)
• Consequence: PFN2 ENST00000494827.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.712

Genes affected

PFN2 (HGNC:8882): (profilin 2) The protein encoded by this gene is a ubiquitous actin monomer-binding protein belonging to the profilin family. It is thought to regulate actin polymerization in response to extracellular signals. There are two alternatively spliced transcript variants encoding different isoforms described for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PFN2	ENST00000494827.5	c.-16+18013A>C		intron_variant		4		ENSP00000418523
PFN2	ENST00000497148.5	c.-15-36057A>C		intron_variant		4		ENSP00000417817
PFN2	ENST00000649949.1	c.-16+16348A>C		intron_variant				ENSP00000498146

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47477 AN: 151800 Hom.: 7461 Cov.: 31

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.297

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.263

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.269

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.290

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.313 AC: 47500 AN: 151918 Hom.: 7460 Cov.: 31 AF XY: 0.313 AC XY: 23224 AN XY: 74252

Gnomad4 AFR AF: 0.351

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.269

Gnomad4 NFE AF: 0.290

Gnomad4 OTH AF: 0.327

Alfa AF: 0.301 Hom.: 4188

Bravo AF: 0.318

Asia WGS AF: 0.308 AC: 1075 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9289798; hg19: chr3-149722394;