6-12933680-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_030948.6(PHACTR1):c.251-119685G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00371 in 1,612,844 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0038 (28 hom.)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0290

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003627181).
• BP6: Variant 6-12933680-G-A is Benign according to our data. Variant chr6-12933680-G-A is described in ClinVar as [Benign]. Clinvar id is 1879646.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 404 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.251-119685G>A		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.251-119685G>A		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.00265 AC: 404 AN: 152224 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00209

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0134

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00292

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.00449 AC: 1085 AN: 241474 Hom.: 7 AF XY: 0.00528 AC XY: 700 AN XY: 132602

Gnomad AFR exome AF: 0.000701

Gnomad AMR exome AF: 0.00116

Gnomad ASJ exome AF: 0.0191

Gnomad EAS exome AF: 0.0000560

Gnomad SAS exome AF: 0.0145

Gnomad FIN exome AF: 0.000325

Gnomad NFE exome AF: 0.00351

Gnomad OTH exome AF: 0.00351

GnomAD4 exome AF: 0.00382 AC: 5573 AN: 1460502 Hom.: 28 Cov.: 31 AF XY: 0.00435 AC XY: 3160 AN XY: 726550

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.00121

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.000126

Gnomad4 SAS exome AF: 0.0147

Gnomad4 FIN exome AF: 0.000363

Gnomad4 NFE exome AF: 0.00297

Gnomad4 OTH exome AF: 0.00499

GnomAD4 genome AF: 0.00265 AC: 403 AN: 152342 Hom.: 2 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74504

Gnomad4 AFR AF: 0.000481

Gnomad4 AMR AF: 0.00209

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0135

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00293

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.00322 Hom.: 1

Bravo AF: 0.00235

TwinsUK AF: 0.00297 AC: 11

ALSPAC AF: 0.00285 AC: 11

ESP6500AA AF: 0.000571 AC: 1

ESP6500EA AF: 0.00477 AC: 19

ExAC AF: 0.00444 AC: 516

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2023

PHACTR1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.56
Cadd	Benign	7.9
Dann	Benign	0.95
DEOGEN2	Benign	0.0077	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.014	N
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.030
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.032	D
Polyphen		0.19	B
Vest4		0.24
MVP		0.37
MPC		0.030
ClinPred		0.0077	T
GERP RS		0.11

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs144313630; hg19: chr6-12933912;