rs9296494

Positions:

• chr6-12859654-G-A
• chr6-12859654-G-T

Variant summary

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

The NM_030948.6(PHACTR1):​c.250+109864G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 151,994 control chromosomes in the GnomAD database, including 30,165 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 0.61 (30165 hom., cov: 31)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.128

Genes affected

PHACTR1 (HGNC:20990): (phosphatase and actin regulator 1) The protein encoded by this gene is a member of the phosphatase and actin regulator family of proteins. This family member can bind actin and regulate the reorganization of the actin cytoskeleton. It plays a role in tubule formation and in endothelial cell survival. Polymorphisms in this gene are associated with susceptibility to myocardial infarction, coronary artery disease and cervical artery dissection. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Apr 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.969 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.250+109864G>A		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.250+109864G>A		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.612 AC: 92884 AN: 151876 Hom.: 30143 Cov.: 31

Gnomad AFR AF: 0.399

Gnomad AMI AF: 0.572

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.612

Gnomad EAS AF: 0.992

Gnomad SAS AF: 0.800

Gnomad FIN AF: 0.779

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.656

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.612 AC: 92946 AN: 151994 Hom.: 30165 Cov.: 31 AF XY: 0.623 AC XY: 46311 AN XY: 74322

Gnomad4 AFR AF: 0.399

Gnomad4 AMR AF: 0.691

Gnomad4 ASJ AF: 0.612

Gnomad4 EAS AF: 0.992

Gnomad4 SAS AF: 0.800

Gnomad4 FIN AF: 0.779

Gnomad4 NFE AF: 0.656

Gnomad4 OTH AF: 0.611

Alfa AF: 0.643 Hom.: 42191

Bravo AF: 0.595

Asia WGS AF: 0.870 AC: 3024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.6
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: rs9296494; hg19: chr6-12859886;