Variant 6-12933680-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0290

Variant links:

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]

PHACTR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 GnomAd4 at 403 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR1	NM_030948.6 linkuse as main transcript	c.251-119685G>A		intron_variant		ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12 linkuse as main transcript	c.251-119685G>A		intron_variant		2	NM_030948.6	ENSP00000329880	P3	Q9C0D0-1

Frequencies

GnomAD3 genomes

AF:

0.00265

AC:

404

AN:

152224

Hom.:

Cov.:

show subpopulations

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.:

AF XY:

0.00528

AC XY:

700

AN XY:

132602

show subpopulations

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.:

Cov.:

AF XY:

0.00435

AC XY:

3160

AN XY:

726550

show subpopulations

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.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74504

show subpopulations

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.:

Bravo

AF:

0.00235

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.000571

AC:

ESP6500EA

AF:

0.00477

AC:

ExAC

AF:

0.00444

AC:

516

Asia WGS

AF:

0.00635

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

PHACTR1: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.9

DANN

Benign

0.95

DEOGEN2

Benign

0.0077

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.014

MetaRNN

Benign

0.0036

MetaSVM

Benign

-1.0

MutationTaster

Benign

1.0

N;N;N

PROVEAN

Benign

-0.25

REVEL

Benign

0.030

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.032

Polyphen

0.19

Vest4

0.24

MVP

0.37

MPC

0.030

ClinPred

0.0077

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over