NM_030948.6:c.251-127661C>A

Variant names:

• chr6-12925704-C-A
• rs1953088
• NM_030948.6:c.251-127661C>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.251-127661C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.517 in 152,016 control chromosomes in the GnomAD database, including 23,309 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 0.52 (23309 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.261
• Publications: 10 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 (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.251-127661C>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.251-127661C>A		intron_variant	Intron 4 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78645 AN: 151898 Hom.: 23296 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.544

Gnomad AMR AF: 0.575

Gnomad ASJ AF: 0.567

Gnomad EAS AF: 0.909

Gnomad SAS AF: 0.674

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.512

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

GnomAD4 genome AF: 0.517 AC: 78667 AN: 152016 Hom.: 23309 Cov.: 32 AF XY: 0.526 AC XY: 39063 AN XY: 74292

African (AFR) AF: 0.213 AC: 8852 AN: 41490

American (AMR) AF: 0.575 AC: 8777 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 1964 AN: 3466

East Asian (EAS) AF: 0.909 AC: 4679 AN: 5146

South Asian (SAS) AF: 0.674 AC: 3244 AN: 4810

European-Finnish (FIN) AF: 0.677 AC: 7145 AN: 10550

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.622 AC: 42276 AN: 67972

Other (OTH) AF: 0.519 AC: 1093 AN: 2106

Alfa AF: 0.508 Hom.: 3307

Bravo AF: 0.494

Asia WGS AF: 0.744 AC: 2585 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	0.63
DANN	Benign	0.47
PhyloP100		-0.26
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: rs1953088; hg19: chr6-12925936;