chr6-12934070-G-C

Position:

• chr6-12934070-G-C

Variant summary

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

The NM_030948.6(PHACTR1):​c.251-119295G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,272,886 control chromosomes in the GnomAD database, including 97,613 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 0.48 (20189 hom., cov: 31)
  • Exomes 𝑓: 0.36 (77424 hom.)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.769 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.251-119295G>C		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.251-119295G>C		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72795 AN: 151862 Hom.: 20134 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.361 AC: 404798 AN: 1120906 Hom.: 77424 AF XY: 0.357 AC XY: 196092 AN XY: 549048

Gnomad4 AFR exome AF: 0.794

Gnomad4 AMR exome AF: 0.405

Gnomad4 ASJ exome AF: 0.424

Gnomad4 EAS exome AF: 0.250

Gnomad4 SAS exome AF: 0.234

Gnomad4 FIN exome AF: 0.348

Gnomad4 NFE exome AF: 0.359

Gnomad4 OTH exome AF: 0.374

GnomAD4 genome AF: 0.480 AC: 72909 AN: 151980 Hom.: 20189 Cov.: 31 AF XY: 0.473 AC XY: 35116 AN XY: 74280

Gnomad4 AFR AF: 0.776

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.361

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.473

Alfa AF: 0.275 Hom.: 683

Bravo AF: 0.504

Asia WGS AF: 0.254 AC: 885 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.42

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: rs6458545; hg19: chr6-12934302;