6-12825642-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_030948.6(PHACTR1):c.250+75852C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,064 control chromosomes in the GnomAD database, including 11,179 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 0.35 (11179 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.250+75852C>T		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.250+75852C>T		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52569 AN: 151946 Hom.: 11175 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.346 AC: 52567 AN: 152064 Hom.: 11179 Cov.: 32 AF XY: 0.353 AC XY: 26207 AN XY: 74324

Gnomad4 AFR AF: 0.0874

Gnomad4 AMR AF: 0.387

Gnomad4 ASJ AF: 0.356

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.481

Gnomad4 FIN AF: 0.542

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.334

Alfa AF: 0.402 Hom.: 2890

Bravo AF: 0.322

Asia WGS AF: 0.440 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	2.6
Dann	Benign	0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2026458; hg19: chr6-12825874;