NM_030948.6:c.1392-4881A>G

Variant names:

• chr6-13267979-A-G
• rs202072
• NM_030948.6:c.1392-4881A>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.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
• Publications: 9 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]

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]

TBC1D7 Gene-Disease associations (from GenCC):

• macrocephaly/megalencephaly syndrome, autosomal recessive

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.1392-4881A>G		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.1392-4881A>G		intron_variant	Intron 10 of 14	2	NM_030948.6	ENSP00000329880.8

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

African (AFR) AF: 0.500 AC: 2 AN: 4

American (AMR) AF: 1.00 AC: 2 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.837 AC: 72 AN: 86

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.497 AC: 20532 AN: 41294

American (AMR) AF: 0.825 AC: 12587 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.795 AC: 2758 AN: 3468

East Asian (EAS) AF: 0.494 AC: 2539 AN: 5136

South Asian (SAS) AF: 0.820 AC: 3948 AN: 4812

European-Finnish (FIN) AF: 0.796 AC: 8359 AN: 10496

Middle Eastern (MID) AF: 0.833 AC: 245 AN: 294

European-Non Finnish (NFE) AF: 0.857 AC: 58236 AN: 67984

Other (OTH) AF: 0.756 AC: 1592 AN: 2106

Alfa AF: 0.816 Hom.: 163477

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
PhyloP100		-0.091
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: rs202072; hg19: chr6-13268211;