chr6-12842053-A-G

Position:

• chr6-12842053-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.250+92263A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,082 control chromosomes in the GnomAD database, including 2,776 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 0.19 (2776 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25

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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.244 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.250+92263A>G		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.250+92263A>G		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28112 AN: 151964 Hom.: 2758 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.0789

Gnomad AMR AF: 0.191

Gnomad ASJ AF: 0.151

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.156

Gnomad OTH AF: 0.169

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

GnomAD4 genome AF: 0.185 AC: 28174 AN: 152082 Hom.: 2776 Cov.: 32 AF XY: 0.186 AC XY: 13837 AN XY: 74334

Gnomad4 AFR AF: 0.248

Gnomad4 AMR AF: 0.191

Gnomad4 ASJ AF: 0.151

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.165

Gnomad4 FIN AF: 0.153

Gnomad4 NFE AF: 0.156

Gnomad4 OTH AF: 0.174

Alfa AF: 0.181 Hom.: 462

Bravo AF: 0.193

Asia WGS AF: 0.213 AC: 735 AN: 3458

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.0
DANN	Benign	0.74

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: rs9349350; hg19: chr6-12842285;