6-12907359-A-G

Position:

• chr6-12907359-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030948.6(PHACTR1):​c.251-146006A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,074 control chromosomes in the GnomAD database, including 24,066 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 0.53 (24066 hom., cov: 33)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.461

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.889 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.251-146006A>G		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.251-146006A>G		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80968 AN: 151956 Hom.: 24059 Cov.: 33

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.583

Gnomad ASJ AF: 0.570

Gnomad EAS AF: 0.911

Gnomad SAS AF: 0.683

Gnomad FIN AF: 0.664

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.627

Gnomad OTH AF: 0.528

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

GnomAD4 genome AF: 0.533 AC: 80991 AN: 152074 Hom.: 24066 Cov.: 33 AF XY: 0.540 AC XY: 40163 AN XY: 74322

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.583

Gnomad4 ASJ AF: 0.570

Gnomad4 EAS AF: 0.911

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.664

Gnomad4 NFE AF: 0.627

Gnomad4 OTH AF: 0.531

Alfa AF: 0.606 Hom.: 15208

Bravo AF: 0.512

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.67
DANN	Benign	0.46

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: rs2327620; hg19: chr6-12907591;