chr6-12849072-A-G

Variant names:

• chr6-12849072-A-G
• rs9296488
• NM_030948.6:c.250+99282A>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+99282A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,088 control chromosomes in the GnomAD database, including 3,230 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 0.20 (3230 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.250+99282A>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+99282A>G		intron_variant	Intron 4 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29768 AN: 151970 Hom.: 3207 Cov.: 32

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.194

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.166

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.196 AC: 29833 AN: 152088 Hom.: 3230 Cov.: 32 AF XY: 0.196 AC XY: 14607 AN XY: 74360

African (AFR) AF: 0.285 AC: 11836 AN: 41466

American (AMR) AF: 0.195 AC: 2979 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 558 AN: 3470

East Asian (EAS) AF: 0.179 AC: 927 AN: 5172

South Asian (SAS) AF: 0.166 AC: 801 AN: 4824

European-Finnish (FIN) AF: 0.153 AC: 1621 AN: 10582

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

European-Non Finnish (NFE) AF: 0.156 AC: 10614 AN: 67978

Other (OTH) AF: 0.184 AC: 388 AN: 2114

Alfa AF: 0.190 Hom.: 537

Bravo AF: 0.205

Asia WGS AF: 0.217 AC: 753 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.5
DANN	Benign	0.74
PhyloP100		-1.1
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: rs9296488; hg19: chr6-12849304;