6-12903203-C-T

Variant names:

• chr6-12903203-C-T
• rs4714955
• NM_030948.6:c.251-150162C>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.251-150162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,818 control chromosomes in the GnomAD database, including 6,169 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 0.26 (6169 hom., cov: 31)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.251-150162C>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.251-150162C>T		intron_variant	Intron 4 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39900 AN: 151700 Hom.: 6161 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.263 AC: 39908 AN: 151818 Hom.: 6169 Cov.: 31 AF XY: 0.259 AC XY: 19213 AN XY: 74198

African (AFR) AF: 0.128 AC: 5311 AN: 41398

American (AMR) AF: 0.324 AC: 4934 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.384 AC: 1332 AN: 3470

East Asian (EAS) AF: 0.0147 AC: 76 AN: 5166

South Asian (SAS) AF: 0.183 AC: 880 AN: 4800

European-Finnish (FIN) AF: 0.301 AC: 3167 AN: 10530

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.340 AC: 23078 AN: 67912

Other (OTH) AF: 0.295 AC: 620 AN: 2102

Alfa AF: 0.291 Hom.: 10224

Bravo AF: 0.262

Asia WGS AF: 0.109 AC: 383 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.69
DANN	Benign	0.42
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4714955; hg19: chr6-12903435;