rs1953088

chr6-12925704-C-A

Variant summary

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

The NM_030948.6(PHACTR1):c.251-127661C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,016 control chromosomes in the GnomAD database, including 23,309 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 0.52 (23309 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.251-127661C>A		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.251-127661C>A		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78645 AN: 151898 Hom.: 23296 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.517 AC: 78667 AN: 152016 Hom.: 23309 Cov.: 32 AF XY: 0.526 AC XY: 39063 AN XY: 74292

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.575

Gnomad4 ASJ AF: 0.567

Gnomad4 EAS AF: 0.909

Gnomad4 SAS AF: 0.674

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.622

Gnomad4 OTH AF: 0.519

Alfa AF: 0.518 Hom.: 3290

Bravo AF: 0.494

Asia WGS AF: 0.744 AC: 2585 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	0.63
Dann	Benign	0.47

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: rs1953088; hg19: chr6-12925936;