6-12903725-A-G

Variant names:

• chr6-12903725-A-G
• rs9349379
• NM_030948.6:c.251-149640A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030948.6(PHACTR1):​c.251-149640A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 152,212 control chromosomes in the GnomAD database, including 10,085 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.33 (10085 hom., cov: 33)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.76
• Publications: 297 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 6-12903725-A-G is Benign according to our data. Variant chr6-12903725-A-G is described in ClinVar as Benign. ClinVar VariationId is 1289844.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 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.251-149640A>G		intron	N/A	NP_112210.1
	PHACTR1	NM_001374584.1		c.*1008A>G		3_prime_UTR	Exon 4 of 4	NP_001361513.1
	PHACTR1	NM_001322310.2		c.251-149640A>G		intron	N/A	NP_001309239.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.251-149640A>G		intron	N/A	ENSP00000329880.8
	PHACTR1	ENST00000379348.3	TSL:1	n.428-29908A>G		intron	N/A
	PHACTR1	ENST00000690071.1		n.1491A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49561 AN: 152094 Hom.: 10077 Cov.: 33

Gnomad AFR AF: 0.0823

Gnomad AMI AF: 0.300

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.674

Gnomad SAS AF: 0.518

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.325

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.327

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

GnomAD4 genome AF: 0.326 AC: 49560 AN: 152212 Hom.: 10085 Cov.: 33 AF XY: 0.333 AC XY: 24778 AN XY: 74380

African (AFR) AF: 0.0822 AC: 3414 AN: 41558

American (AMR) AF: 0.348 AC: 5327 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 1440 AN: 3472

East Asian (EAS) AF: 0.674 AC: 3489 AN: 5174

South Asian (SAS) AF: 0.518 AC: 2495 AN: 4818

European-Finnish (FIN) AF: 0.443 AC: 4686 AN: 10570

Middle Eastern (MID) AF: 0.329 AC: 96 AN: 292

European-Non Finnish (NFE) AF: 0.406 AC: 27634 AN: 68000

Other (OTH) AF: 0.333 AC: 705 AN: 2114

Alfa AF: 0.386 Hom.: 53834

Bravo AF: 0.305

Asia WGS AF: 0.527 AC: 1830 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 23, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 30354304)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.9
DANN	Benign	0.86
PhyloP100		1.8
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: rs9349379; hg19: chr6-12903957;