6-12960988-A-G

Variant names:

• chr6-12960988-A-G
• rs6906890
• NM_030948.6:c.251-92377A>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.251-92377A>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
• Publications: 6 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

LOC124901262 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.251-92377A>G		intron	N/A	NP_112210.1
	PHACTR1	NM_001322310.2		c.251-92377A>G		intron	N/A	NP_001309239.1
	PHACTR1	NM_001374581.2		c.251-92377A>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.251-92377A>G		intron	N/A	ENSP00000329880.8
	PHACTR1	ENST00000674595.1		c.251-92377A>G		intron	N/A	ENSP00000502157.1
	PHACTR1	ENST00000674637.1		c.251-92377A>G		intron	N/A	ENSP00000501634.1

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

African (AFR) AF: 0.360 AC: 14922 AN: 41464

American (AMR) AF: 0.163 AC: 2483 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3470

East Asian (EAS) AF: 0.0964 AC: 499 AN: 5176

South Asian (SAS) AF: 0.213 AC: 1029 AN: 4828

European-Finnish (FIN) AF: 0.125 AC: 1327 AN: 10604

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.163 AC: 11107 AN: 67992

Other (OTH) AF: 0.224 AC: 472 AN: 2108

Alfa AF: 0.161 Hom.: 1626

Bravo AF: 0.228

Asia WGS AF: 0.182 AC: 635 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	9.6
DANN	Benign	0.73
PhyloP100		0.75
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: rs6906890; hg19: chr6-12961220;