rs4715166

Variant names:

• chr6-13215826-A-G
• rs4715166
• NM_030948.6:c.986+9690A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030948.6(PHACTR1):​c.986+9690A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 152,008 control chromosomes in the GnomAD database, including 26,784 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 0.58 (26784 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 18 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), Ambry Genetics, G2P
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.669 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.986+9690A>G		intron_variant	Intron 8 of 14	ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.986+9690A>G		intron_variant	Intron 8 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.578 AC: 87790 AN: 151890 Hom.: 26760 Cov.: 32

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.665

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.490

Gnomad FIN AF: 0.645

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.603

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

GnomAD4 genome AF: 0.578 AC: 87860 AN: 152008 Hom.: 26784 Cov.: 32 AF XY: 0.576 AC XY: 42805 AN XY: 74304

African (AFR) AF: 0.402 AC: 16661 AN: 41448

American (AMR) AF: 0.678 AC: 10341 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2203 AN: 3462

East Asian (EAS) AF: 0.301 AC: 1555 AN: 5162

South Asian (SAS) AF: 0.491 AC: 2366 AN: 4818

European-Finnish (FIN) AF: 0.645 AC: 6816 AN: 10574

Middle Eastern (MID) AF: 0.626 AC: 184 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45855 AN: 67970

Other (OTH) AF: 0.604 AC: 1274 AN: 2110

Alfa AF: 0.641 Hom.: 126035

Bravo AF: 0.577

Asia WGS AF: 0.403 AC: 1402 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.41
DANN	Benign	0.66
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4715166; hg19: chr6-13216058;