rs1223531

Variant names:

• chr6-13147303-A-G
• rs1223531
• NM_030948.6:c.416-12901A>G

Variant summary

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

Score: -12 - Benign

-12

BP4_StrongBA1

The NM_030948.6(PHACTR1):​c.416-12901A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.203 in 152,152 control chromosomes in the GnomAD database, including 3,366 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 0.20 (3366 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 2 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

ENSG00000303958 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.416-12901A>G		intron_variant	Intron 5 of 14	ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.416-12901A>G		intron_variant	Intron 5 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30877 AN: 152034 Hom.: 3366 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.233

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.0611

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.255

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.221

Gnomad OTH AF: 0.209

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

GnomAD4 genome AF: 0.203 AC: 30888 AN: 152152 Hom.: 3366 Cov.: 32 AF XY: 0.208 AC XY: 15500 AN XY: 74382

African (AFR) AF: 0.139 AC: 5762 AN: 41520

American (AMR) AF: 0.233 AC: 3552 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 952 AN: 3468

East Asian (EAS) AF: 0.0606 AC: 315 AN: 5194

South Asian (SAS) AF: 0.391 AC: 1887 AN: 4826

European-Finnish (FIN) AF: 0.255 AC: 2696 AN: 10566

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.221 AC: 15032 AN: 67984

Other (OTH) AF: 0.209 AC: 442 AN: 2114

Alfa AF: 0.215 Hom.: 1297

Bravo AF: 0.192

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.3
DANN	Benign	0.40
PhyloP100		-0.073
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: rs1223531; hg19: chr6-13147535;