6-12960988-A-G

Position:

• chr6-12960988-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.251-92377A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,128 control chromosomes in the GnomAD database, including 4,324 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 0.22 (4324 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.751

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]

LOC124901262 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.355 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.251-92377A>G		intron_variant		ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.251-92377A>G		intron_variant		2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.217 AC: 33012 AN: 152010 Hom.: 4325 Cov.: 32

Gnomad AFR AF: 0.360

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.163

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.0968

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.217 AC: 33025 AN: 152128 Hom.: 4324 Cov.: 32 AF XY: 0.213 AC XY: 15856 AN XY: 74394

Gnomad4 AFR AF: 0.360

Gnomad4 AMR AF: 0.163

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.0964

Gnomad4 SAS AF: 0.213

Gnomad4 FIN AF: 0.125

Gnomad4 NFE AF: 0.163

Gnomad4 OTH AF: 0.224

Alfa AF: 0.150 Hom.: 1008

Bravo AF: 0.228

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.73

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: rs6906890; hg19: chr6-12961220;