NM_030948.6:c.250+92263A>G

Variant names:

• chr6-12842053-A-G
• rs9349350
• NM_030948.6:c.250+92263A>G

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+92263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,082 control chromosomes in the GnomAD database, including 2,776 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 0.19 (2776 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 2 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	NM_030948.6	MANE Select	c.250+92263A>G		intron	N/A	NP_112210.1
	PHACTR1	NM_001322310.2		c.250+92263A>G		intron	N/A	NP_001309239.1
	PHACTR1	NM_001374581.2		c.250+92263A>G		intron	N/A	NP_001361510.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.250+92263A>G		intron	N/A	ENSP00000329880.8
	PHACTR1	ENST00000379348.3	TSL:1	n.428-91580A>G		intron	N/A
	PHACTR1	ENST00000674595.1		c.250+92263A>G		intron	N/A	ENSP00000502157.1

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28112 AN: 151964 Hom.: 2758 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.185 AC: 28174 AN: 152082 Hom.: 2776 Cov.: 32 AF XY: 0.186 AC XY: 13837 AN XY: 74334

African (AFR) AF: 0.248 AC: 10304 AN: 41466

American (AMR) AF: 0.191 AC: 2925 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 525 AN: 3470

East Asian (EAS) AF: 0.179 AC: 930 AN: 5182

South Asian (SAS) AF: 0.165 AC: 795 AN: 4820

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10544

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.156 AC: 10599 AN: 67996

Other (OTH) AF: 0.174 AC: 368 AN: 2114

Alfa AF: 0.181 Hom.: 462

Bravo AF: 0.193

Asia WGS AF: 0.213 AC: 735 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.74
PhyloP100		1.3
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: rs9349350; hg19: chr6-12842285;