rs7768030

Variant names:

• chr6-12822741-A-C
• rs7768030
• NM_030948.6:c.250+72951A>C

Your query was ambiguous. Multiple possible variants found:

• chr6-12822741-A-C
• chr6-12822741-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030948.6(PHACTR1):​c.250+72951A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 152,148 control chromosomes in the GnomAD database, including 1,303 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 0.12 (1303 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.255
• Publications: 5 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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.182 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.250+72951A>C		intron	N/A	NP_112210.1
	PHACTR1	NM_001322310.2		c.250+72951A>C		intron	N/A	NP_001309239.1
	PHACTR1	NM_001374581.2		c.250+72951A>C		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.250+72951A>C		intron	N/A	ENSP00000329880.8
	PHACTR1	ENST00000379348.3	TSL:1	n.427+72951A>C		intron	N/A
	PHACTR1	ENST00000674595.1		c.250+72951A>C		intron	N/A	ENSP00000502157.1

Frequencies

GnomAD3 genomes AF: 0.120 AC: 18316 AN: 152030 Hom.: 1285 Cov.: 32

Gnomad AFR AF: 0.186

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.0591

Gnomad EAS AF: 0.180

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0878

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.108

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

GnomAD4 genome AF: 0.121 AC: 18364 AN: 152148 Hom.: 1303 Cov.: 32 AF XY: 0.121 AC XY: 9006 AN XY: 74390

African (AFR) AF: 0.186 AC: 7711 AN: 41478

American (AMR) AF: 0.129 AC: 1975 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0591 AC: 205 AN: 3468

East Asian (EAS) AF: 0.180 AC: 928 AN: 5166

South Asian (SAS) AF: 0.109 AC: 525 AN: 4814

European-Finnish (FIN) AF: 0.0878 AC: 930 AN: 10596

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.0851 AC: 5790 AN: 68006

Other (OTH) AF: 0.114 AC: 240 AN: 2112

Alfa AF: 0.0895 Hom.: 1285

Bravo AF: 0.129

Asia WGS AF: 0.189 AC: 657 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.0
DANN	Benign	0.33
PhyloP100		0.26
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: rs7768030; hg19: chr6-12822973;