NM_030948.6:c.250+138982C>T

Variant names:

• chr6-12888772-C-T
• rs1332844
• NM_030948.6:c.250+138982C>T

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+138982C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.614 in 152,052 control chromosomes in the GnomAD database, including 29,187 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 0.61 (29187 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 36 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.250+138982C>T		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+138982C>T		intron_variant	Intron 4 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.615 AC: 93367 AN: 151934 Hom.: 29168 Cov.: 32

Gnomad AFR AF: 0.533

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.615

Gnomad ASJ AF: 0.578

Gnomad EAS AF: 0.924

Gnomad SAS AF: 0.698

Gnomad FIN AF: 0.667

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.630

Gnomad OTH AF: 0.596

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

GnomAD4 genome AF: 0.614 AC: 93430 AN: 152052 Hom.: 29187 Cov.: 32 AF XY: 0.620 AC XY: 46064 AN XY: 74310

African (AFR) AF: 0.533 AC: 22110 AN: 41462

American (AMR) AF: 0.614 AC: 9388 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.578 AC: 2007 AN: 3470

East Asian (EAS) AF: 0.924 AC: 4792 AN: 5184

South Asian (SAS) AF: 0.698 AC: 3363 AN: 4820

European-Finnish (FIN) AF: 0.667 AC: 7041 AN: 10556

Middle Eastern (MID) AF: 0.510 AC: 150 AN: 294

European-Non Finnish (NFE) AF: 0.630 AC: 42812 AN: 67962

Other (OTH) AF: 0.599 AC: 1266 AN: 2114

Alfa AF: 0.626 Hom.: 124948

Bravo AF: 0.604

Asia WGS AF: 0.755 AC: 2627 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	2.1
DANN	Benign	0.54
PhyloP100		-0.30
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: rs1332844; hg19: chr6-12889004;