6-13225739-G-A

Variant names:

• chr6-13225739-G-A
• rs12195574
• NM_030948.6:c.987-2077G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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), G2P, Ambry Genetics
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000303988 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	NM_030948.6	MANE Select	c.987-2077G>A		intron	N/A	NP_112210.1	Q9C0D0-1
	PHACTR1	NM_001322314.4		c.1197-2077G>A		intron	N/A	NP_001309243.1	A0A6Q8PGC2
	PHACTR1	NM_001322310.2		c.1194-2077G>A		intron	N/A	NP_001309239.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.987-2077G>A		intron	N/A	ENSP00000329880.8	Q9C0D0-1
	PHACTR1	ENST00000675203.2		c.1197-2077G>A		intron	N/A	ENSP00000502172.2	A0A6Q8PGC2
	PHACTR1	ENST00000674595.1		c.987-2077G>A		intron	N/A	ENSP00000502157.1	A0A6Q8PG87

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

African (AFR) AF: 0.0708 AC: 2938 AN: 41496

American (AMR) AF: 0.0205 AC: 313 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0380 AC: 132 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5176

South Asian (SAS) AF: 0.0199 AC: 96 AN: 4826

European-Finnish (FIN) AF: 0.0350 AC: 370 AN: 10574

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0565 AC: 3839 AN: 68000

Other (OTH) AF: 0.0455 AC: 96 AN: 2112

Alfa AF: 0.0499 Hom.: 101

Bravo AF: 0.0507

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.075
DANN	Benign	0.58
PhyloP100		-2.0
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: rs12195574; hg19: chr6-13225971;