rs12195574

Positions:

• chr6-13225739-G-A

Variant summary

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

The NM_030948.6(PHACTR1):​c.987-2077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0515 in 152,164 control chromosomes in the GnomAD database, including 227 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 0.051 (227 hom., cov: 33)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96

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]

LOC105374933 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0687 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.987-2077G>A		intron_variant		ENST00000332995.12	NP_112210.1
LOC105374933	XR_007059456.1	n.2541+678C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.987-2077G>A		intron_variant		2	NM_030948.6	ENSP00000329880	P3

Frequencies

GnomAD3 genomes AF: 0.0515 AC: 7826 AN: 152046 Hom.: 226 Cov.: 33

Gnomad AFR AF: 0.0709

Gnomad AMI AF: 0.0428

Gnomad AMR AF: 0.0206

Gnomad ASJ AF: 0.0380

Gnomad EAS AF: 0.000771

Gnomad SAS AF: 0.0195

Gnomad FIN AF: 0.0350

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0565

Gnomad OTH AF: 0.0464

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

GnomAD4 genome AF: 0.0515 AC: 7829 AN: 152164 Hom.: 227 Cov.: 33 AF XY: 0.0491 AC XY: 3650 AN XY: 74402

Gnomad4 AFR AF: 0.0708

Gnomad4 AMR AF: 0.0205

Gnomad4 ASJ AF: 0.0380

Gnomad4 EAS AF: 0.000773

Gnomad4 SAS AF: 0.0199

Gnomad4 FIN AF: 0.0350

Gnomad4 NFE AF: 0.0565

Gnomad4 OTH AF: 0.0455

Alfa AF: 0.0534 Hom.: 50

Bravo AF: 0.0507

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.075
DANN	Benign	0.58

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: rs12195574; hg19: chr6-13225971;