NM_030948.6:c.250+98947T>G

Variant names:

• chr6-12848737-T-G
• rs9296486
• NM_030948.6:c.250+98947T>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+98947T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,154 control chromosomes in the GnomAD database, including 2,929 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 (2929 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.730
• Publications: 4 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=-0.58).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.257 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.250+98947T>G		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+98947T>G		intron_variant	Intron 4 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28715 AN: 152036 Hom.: 2911 Cov.: 32

Gnomad AFR AF: 0.261

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.174

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

GnomAD4 genome AF: 0.189 AC: 28775 AN: 152154 Hom.: 2929 Cov.: 32 AF XY: 0.190 AC XY: 14111 AN XY: 74374

African (AFR) AF: 0.261 AC: 10839 AN: 41494

American (AMR) AF: 0.192 AC: 2942 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3472

East Asian (EAS) AF: 0.179 AC: 929 AN: 5178

South Asian (SAS) AF: 0.166 AC: 800 AN: 4826

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10582

Middle Eastern (MID) AF: 0.130 AC: 38 AN: 292

European-Non Finnish (NFE) AF: 0.156 AC: 10602 AN: 67990

Other (OTH) AF: 0.178 AC: 377 AN: 2114

Alfa AF: 0.169 Hom.: 1268

Bravo AF: 0.197

Asia WGS AF: 0.215 AC: 747 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.68
PhyloP100		0.73
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: rs9296486; hg19: chr6-12848969;