NM_030948.6:c.251-130908G>A

Variant names:

• chr6-12922457-G-A
• rs2327621
• NM_030948.6:c.251-130908G>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.251-130908G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,768 control chromosomes in the GnomAD database, including 33,566 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 0.66 (33566 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 8 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.963 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.251-130908G>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.251-130908G>A		intron_variant	Intron 4 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100250 AN: 151650 Hom.: 33531 Cov.: 32

Gnomad AFR AF: 0.613

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.614

Gnomad EAS AF: 0.986

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.715

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.654

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.661 AC: 100330 AN: 151768 Hom.: 33566 Cov.: 32 AF XY: 0.668 AC XY: 49555 AN XY: 74140

African (AFR) AF: 0.613 AC: 25346 AN: 41370

American (AMR) AF: 0.646 AC: 9815 AN: 15188

Ashkenazi Jewish (ASJ) AF: 0.614 AC: 2130 AN: 3470

East Asian (EAS) AF: 0.985 AC: 5104 AN: 5180

South Asian (SAS) AF: 0.818 AC: 3928 AN: 4800

European-Finnish (FIN) AF: 0.715 AC: 7538 AN: 10546

Middle Eastern (MID) AF: 0.616 AC: 181 AN: 294

European-Non Finnish (NFE) AF: 0.654 AC: 44412 AN: 67900

Other (OTH) AF: 0.649 AC: 1371 AN: 2112

Alfa AF: 0.640 Hom.: 8310

Bravo AF: 0.649

Asia WGS AF: 0.876 AC: 3041 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.4
DANN	Benign	0.70
PhyloP100		0.29
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: rs2327621; hg19: chr6-12922689;