chr6-12901209-C-A

Variant names:

• chr6-12901209-C-A
• rs9369640
• NM_030948.6:c.250+151419C>A

Variant summary

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

The NM_030948.6(PHACTR1):​c.250+151419C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,940 control chromosomes in the GnomAD database, including 26,121 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 0.57 (26121 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.867
• Publications: 47 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=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.250+151419C>A		intron_variant	Intron 4 of 14	ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.250+151419C>A		intron_variant	Intron 4 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.566 AC: 86003 AN: 151822 Hom.: 26114 Cov.: 32

Gnomad AFR AF: 0.351

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.599

Gnomad ASJ AF: 0.581

Gnomad EAS AF: 0.959

Gnomad SAS AF: 0.787

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.555

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

GnomAD4 genome AF: 0.566 AC: 86037 AN: 151940 Hom.: 26121 Cov.: 32 AF XY: 0.576 AC XY: 42742 AN XY: 74262

African (AFR) AF: 0.351 AC: 14512 AN: 41394

American (AMR) AF: 0.598 AC: 9135 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.581 AC: 2015 AN: 3468

East Asian (EAS) AF: 0.959 AC: 4950 AN: 5162

South Asian (SAS) AF: 0.787 AC: 3792 AN: 4818

European-Finnish (FIN) AF: 0.678 AC: 7154 AN: 10554

Middle Eastern (MID) AF: 0.500 AC: 145 AN: 290

European-Non Finnish (NFE) AF: 0.628 AC: 42654 AN: 67972

Other (OTH) AF: 0.561 AC: 1183 AN: 2110

Alfa AF: 0.610 Hom.: 124188

Bravo AF: 0.545

Asia WGS AF: 0.835 AC: 2903 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.010
DANN	Benign	0.62
PhyloP100		-0.87
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: rs9369640; hg19: chr6-12901441;