rs1223531

Positions:

• chr6-13147303-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.416-12901A>G		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.416-12901A>G		intron_variant		2	NM_030948.6	P3

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.233

Gnomad4 ASJ AF: 0.275

Gnomad4 EAS AF: 0.0606

Gnomad4 SAS AF: 0.391

Gnomad4 FIN AF: 0.255

Gnomad4 NFE AF: 0.221

Gnomad4 OTH AF: 0.209

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1223531; hg19: chr6-13147535;