chr6-13222645-T-C

Variant names:

• chr6-13222645-T-C
• rs4711939
• NM_030948.6:c.987-5171T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030948.6(PHACTR1):​c.987-5171T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.622 in 152,118 control chromosomes in the GnomAD database, including 30,310 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 0.62 (30310 hom., cov: 33)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.694 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.987-5171T>C		intron_variant	Intron 8 of 14	ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.987-5171T>C		intron_variant	Intron 8 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94487 AN: 152002 Hom.: 30287 Cov.: 33

Gnomad AFR AF: 0.502

Gnomad AMI AF: 0.686

Gnomad AMR AF: 0.705

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.699

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.622 AC: 94556 AN: 152118 Hom.: 30310 Cov.: 33 AF XY: 0.617 AC XY: 45927 AN XY: 74380

African (AFR) AF: 0.502 AC: 20845 AN: 41486

American (AMR) AF: 0.705 AC: 10783 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3468

East Asian (EAS) AF: 0.288 AC: 1492 AN: 5182

South Asian (SAS) AF: 0.538 AC: 2597 AN: 4824

European-Finnish (FIN) AF: 0.638 AC: 6749 AN: 10580

Middle Eastern (MID) AF: 0.682 AC: 199 AN: 292

European-Non Finnish (NFE) AF: 0.699 AC: 47526 AN: 67982

Other (OTH) AF: 0.641 AC: 1351 AN: 2108

Alfa AF: 0.562 Hom.: 1952

Bravo AF: 0.624

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.090
DANN	Benign	0.84
PhyloP100		-1.8
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: rs4711939; hg19: chr6-13222877;