NM_030948.6:c.1392-2147G>C

Variant names:

• chr6-13270713-G-C
• rs1223397
• NM_030948.6:c.1392-2147G>C

Variant summary

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

The NM_030948.6(PHACTR1):​c.1392-2147G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 152,138 control chromosomes in the GnomAD database, including 2,822 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 0.19 (2822 hom., cov: 32)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.319 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.1392-2147G>C		intron_variant	Intron 10 of 14	ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.1392-2147G>C		intron_variant	Intron 10 of 14	2	NM_030948.6	ENSP00000329880.8

Frequencies

GnomAD3 genomes AF: 0.189 AC: 28754 AN: 152022 Hom.: 2825 Cov.: 32

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.171

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.262

Gnomad SAS AF: 0.333

Gnomad FIN AF: 0.167

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.184

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

GnomAD4 genome AF: 0.189 AC: 28765 AN: 152138 Hom.: 2822 Cov.: 32 AF XY: 0.191 AC XY: 14193 AN XY: 74352

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.201

Gnomad4 EAS AF: 0.262

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.167

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.184

Alfa AF: 0.182 Hom.: 1484

Bravo AF: 0.184

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.52
DANN	Benign	0.55

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: rs1223397; hg19: chr6-13270945;