Genetic Variant PHACTR1:c.251-119685G>A (chr6-12933680-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

developmental and epileptic encephalopathy, 70
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

PHACTR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 1879646.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 403 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030948.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHACTR1	NM_030948.6	MANE Select	c.251-119685G>A	intron	N/A	NP_112210.1	Q9C0D0-1
PHACTR1	NM_001322310.2		c.251-119685G>A	intron	N/A	NP_001309239.1
PHACTR1	NM_001374581.2		c.251-119685G>A	intron	N/A	NP_001361510.1	A0A6Q8PG87

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.251-119685G>A	intron	N/A	ENSP00000329880.8	Q9C0D0-1
PHACTR1	ENST00000379348.3	TSL:1	n.475G>A	non_coding_transcript_exon	Exon 4 of 4
PHACTR1	ENST00000674595.1		c.251-119685G>A	intron	N/A	ENSP00000502157.1	A0A6Q8PG87

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

GnomAD2 exomes

AF:

0.00449

AC:

1085

AN:

241474

AF XY:

0.00528

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 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

African (AFR)

AF:

0.000568

AC:

AN:

33468

American (AMR)

AF:

0.00121

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.0201

AC:

524

AN:

26128

East Asian (EAS)

AF:

0.000126

AC:

AN:

39700

South Asian (SAS)

AF:

0.0147

AC:

1271

AN:

86258

European-Finnish (FIN)

AF:

0.000363

AC:

AN:

52292

Middle Eastern (MID)

AF:

0.0142

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00297

AC:

3298

AN:

1111810

Other (OTH)

AF:

0.00499

AC:

301

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

381

762

1142

1523

1904

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

136

272

408

544

680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00265

AC:

403

AN:

152342

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74504

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41578

American (AMR)

AF:

0.00209

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.0135

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00293

AC:

199

AN:

68030

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

7.9

(source)

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

PhyloP100

-0.029

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

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over