6-12903725-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030948.6(PHACTR1):c.251-149640A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,212 control chromosomes in the GnomAD database, including 10,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (10085 hom., cov: 33)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-12903725-A-G is Benign according to our data. Variant chr6-12903725-A-G is described in ClinVar as [Benign]. Clinvar id is 1289844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.251-149640A>G		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.251-149640A>G		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49561 AN: 152094 Hom.: 10077 Cov.: 33

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.326 AC: 49560 AN: 152212 Hom.: 10085 Cov.: 33 AF XY: 0.333 AC XY: 24778 AN XY: 74380

Gnomad4 AFR AF: 0.0822

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.674

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.443

Gnomad4 NFE AF: 0.406

Gnomad4 OTH AF: 0.333

Alfa AF: 0.401 Hom.: 28495

Bravo AF: 0.305

Asia WGS AF: 0.527 AC: 1830 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 23, 2019

This variant is associated with the following publications: (PMID: 30354304) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.9
Dann	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs9349379; hg19: chr6-12903957;