6-12907359-A-G

Variant names:

• chr6-12907359-A-G
• rs2327620
• NM_030948.6:c.251-146006A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 9 publications found

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]

PHACTR1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 70

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030948.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	NM_030948.6	MANE Select	c.251-146006A>G		intron	N/A	NP_112210.1
	PHACTR1	NM_001322310.2		c.251-146006A>G		intron	N/A	NP_001309239.1
	PHACTR1	NM_001374581.2		c.251-146006A>G		intron	N/A	NP_001361510.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.251-146006A>G		intron	N/A	ENSP00000329880.8
	PHACTR1	ENST00000379348.3	TSL:1	n.428-26274A>G		intron	N/A
	PHACTR1	ENST00000674595.1		c.251-146006A>G		intron	N/A	ENSP00000502157.1

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

African (AFR) AF: 0.258 AC: 10720 AN: 41512

American (AMR) AF: 0.583 AC: 8902 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.570 AC: 1978 AN: 3472

East Asian (EAS) AF: 0.911 AC: 4697 AN: 5156

South Asian (SAS) AF: 0.682 AC: 3288 AN: 4820

European-Finnish (FIN) AF: 0.664 AC: 7013 AN: 10562

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.627 AC: 42634 AN: 67958

Other (OTH) AF: 0.531 AC: 1121 AN: 2110

Alfa AF: 0.563 Hom.: 17434

Bravo AF: 0.512

Asia WGS AF: 0.734 AC: 2551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.67
DANN	Benign	0.46
PhyloP100		-0.46
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2327620; hg19: chr6-12907591;