6-12934070-G-C

Variant names:

• chr6-12934070-G-C
• rs6458545
• NM_030948.6:c.251-119295G>C

Variant summary

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

The NM_030948.6(PHACTR1):​c.251-119295G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.375 in 1,272,886 control chromosomes in the GnomAD database, including 97,613 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 0.48 (20189 hom., cov: 31)
  • Exomes 𝑓: 0.36 (77424 hom.)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.385
• Publications: 12 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

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 = 0.769 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.251-119295G>C		intron	N/A	NP_112210.1	Q9C0D0-1
	PHACTR1	NM_001322310.2		c.251-119295G>C		intron	N/A	NP_001309239.1
	PHACTR1	NM_001374581.2		c.251-119295G>C		intron	N/A	NP_001361510.1	A0A6Q8PG87

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PHACTR1	ENST00000332995.12	TSL:2 MANE Select	c.251-119295G>C		intron	N/A	ENSP00000329880.8	Q9C0D0-1
	PHACTR1	ENST00000379348.3	TSL:1	n.865G>C		non_coding_transcript_exon	Exon 4 of 4
	PHACTR1	ENST00000674595.1		c.251-119295G>C		intron	N/A	ENSP00000502157.1	A0A6Q8PG87

Frequencies

GnomAD3 genomes AF: 0.479 AC: 72795 AN: 151862 Hom.: 20134 Cov.: 31

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.455

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.224

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.476

GnomAD4 exome AF: 0.361 AC: 404798 AN: 1120906 Hom.: 77424 AF XY: 0.357 AC XY: 196092 AN XY: 549048

African (AFR) AF: 0.794 AC: 19784 AN: 24910

American (AMR) AF: 0.405 AC: 8031 AN: 19808

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 7399 AN: 17468

East Asian (EAS) AF: 0.250 AC: 8143 AN: 32558

South Asian (SAS) AF: 0.234 AC: 13719 AN: 58564

European-Finnish (FIN) AF: 0.348 AC: 10869 AN: 31204

Middle Eastern (MID) AF: 0.455 AC: 1459 AN: 3210

European-Non Finnish (NFE) AF: 0.359 AC: 317636 AN: 885756

Other (OTH) AF: 0.374 AC: 17758 AN: 47428

GnomAD4 genome AF: 0.480 AC: 72909 AN: 151980 Hom.: 20189 Cov.: 31 AF XY: 0.473 AC XY: 35116 AN XY: 74280

African (AFR) AF: 0.776 AC: 32156 AN: 41458

American (AMR) AF: 0.428 AC: 6532 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 1451 AN: 3464

East Asian (EAS) AF: 0.219 AC: 1132 AN: 5160

South Asian (SAS) AF: 0.224 AC: 1082 AN: 4820

European-Finnish (FIN) AF: 0.361 AC: 3806 AN: 10552

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25193 AN: 67938

Other (OTH) AF: 0.473 AC: 999 AN: 2112

Alfa AF: 0.275 Hom.: 683

Bravo AF: 0.504

Asia WGS AF: 0.254 AC: 885 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	0.69
DANN	Benign	0.42
PhyloP100		-0.39
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: rs6458545; hg19: chr6-12934302;