6-13267979-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030948.6(PHACTR1):c.1392-4881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.735 in 151,864 control chromosomes in the GnomAD database, including 42,943 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 0.73 (42908 hom., cov: 30)
  • Exomes 𝑓: 0.78 (35 hom.)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0910

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]

TBC1D7-LOC100130357 (HGNC:):

TBC1D7 (HGNC:21066): (TBC1 domain family member 7) This gene encodes a member of the TBC-domain containing protein family. The encoded protein functions as a subunit of the tuberous sclerosis TSC1-TSC2 complex which plays a role in the regulation of cellular growth and differentiation. Mutations in this gene have been associated with autosomal recessive megalencephaly. Alternative splicing results in multiple transcript variants. Naturally occurring readthrough transcription occurs between this locus and downstream LOC100130357. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.851 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PHACTR1	NM_030948.6	c.1392-4881A>G		intron_variant		ENST00000332995.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PHACTR1	ENST00000332995.12	c.1392-4881A>G		intron_variant		2	NM_030948.6	P3

Frequencies

GnomAD3 genomes AF: 0.735 AC: 111461 AN: 151648 Hom.: 42887 Cov.: 30

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.800

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.795

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.835

Gnomad NFE AF: 0.857

Gnomad OTH AF: 0.759

GnomAD4 exome AF: 0.780 AC: 78 AN: 100 Hom.: 35 AF XY: 0.750 AC XY: 57 AN XY: 76

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.837

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.735 AC: 111526 AN: 151764 Hom.: 42908 Cov.: 30 AF XY: 0.735 AC XY: 54498 AN XY: 74126

Gnomad4 AFR AF: 0.497

Gnomad4 AMR AF: 0.825

Gnomad4 ASJ AF: 0.795

Gnomad4 EAS AF: 0.494

Gnomad4 SAS AF: 0.820

Gnomad4 FIN AF: 0.796

Gnomad4 NFE AF: 0.857

Gnomad4 OTH AF: 0.756

Alfa AF: 0.837 Hom.: 107621

Bravo AF: 0.724

Asia WGS AF: 0.665 AC: 2313 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
Cadd	Benign	2.3
Dann	Benign	0.83

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

Publications

LitVar

Other links and lift over

dbSNP: rs202072; hg19: chr6-13268211;