6-12825642-C-T

Variant names:

• chr6-12825642-C-T
• rs2026458
• NM_030948.6:c.250+75852C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_030948.6(PHACTR1):​c.250+75852C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,064 control chromosomes in the GnomAD database, including 11,179 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 0.35 (11179 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0450
• Publications: 23 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), G2P, Ambry Genetics
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.464 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030948.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	NM_030948.6	MANE Select	c.250+75852C>T		intron	N/A	NP_112210.1	Q9C0D0-1
	PHACTR1	NM_001322310.2		c.250+75852C>T		intron	N/A	NP_001309239.1
	PHACTR1	NM_001374581.2		c.250+75852C>T		intron	N/A	NP_001361510.1	A0A6Q8PG87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.250+75852C>T		intron	N/A	ENSP00000329880.8	Q9C0D0-1
	PHACTR1	ENST00000379348.3	TSL:1	n.427+75852C>T		intron	N/A
	PHACTR1	ENST00000674595.1		c.250+75852C>T		intron	N/A	ENSP00000502157.1	A0A6Q8PG87

Frequencies

GnomAD3 genomes AF: 0.346 AC: 52569 AN: 151946 Hom.: 11175 Cov.: 32

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.356

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.482

Gnomad FIN AF: 0.542

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.446

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.346 AC: 52567 AN: 152064 Hom.: 11179 Cov.: 32 AF XY: 0.353 AC XY: 26207 AN XY: 74324

African (AFR) AF: 0.0874 AC: 3628 AN: 41528

American (AMR) AF: 0.387 AC: 5905 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.356 AC: 1237 AN: 3472

East Asian (EAS) AF: 0.464 AC: 2394 AN: 5156

South Asian (SAS) AF: 0.481 AC: 2313 AN: 4812

European-Finnish (FIN) AF: 0.542 AC: 5720 AN: 10546

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30297 AN: 67970

Other (OTH) AF: 0.334 AC: 707 AN: 2116

Alfa AF: 0.334 Hom.: 6223

Bravo AF: 0.322

Asia WGS AF: 0.440 AC: 1530 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.6
DANN	Benign	0.65
PhyloP100		0.045
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.21		Position offset: -2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2026458; hg19: chr6-12825874;