rs144313630

Variant names:

• chr6-12933680-G-A
• rs144313630
• NM_030948.6:c.251-119685G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-12933680-G-A
• chr6-12933680-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 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

GnomAD2 exomes AF: 0.00449 AC: 1085 AN: 241474 AF XY: 0.00528

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.: 28 Cov.: 31 AF XY: 0.00435 AC XY: 3160 AN XY: 726550

African (AFR) AF: 0.000568 AC: 19 AN: 33468

American (AMR) AF: 0.00121 AC: 54 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0201 AC: 524 AN: 26128

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39700

South Asian (SAS) AF: 0.0147 AC: 1271 AN: 86258

European-Finnish (FIN) AF: 0.000363 AC: 19 AN: 52292

Middle Eastern (MID) AF: 0.0142 AC: 82 AN: 5766

European-Non Finnish (NFE) AF: 0.00297 AC: 3298 AN: 1111810

Other (OTH) AF: 0.00499 AC: 301 AN: 60362

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

African (AFR) AF: 0.000481 AC: 20 AN: 41578

American (AMR) AF: 0.00209 AC: 32 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.0135 AC: 65 AN: 4832

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00293 AC: 199 AN: 68030

Other (OTH) AF: 0.00190 AC: 4 AN: 2110

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

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
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
PhyloP100		-0.029
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
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs144313630; hg19: chr6-12933912;