chr6-12903203-C-T

Position:

• chr6-12903203-C-T

Variant summary

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

The NM_030948.6(PHACTR1):​c.251-150162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,818 control chromosomes in the GnomAD database, including 6,169 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 0.26 (6169 hom., cov: 31)
• Consequence: PHACTR1 NM_030948.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.820

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PHACTR1	NM_030948.6	c.251-150162C>T		intron_variant		ENST00000332995.12	NP_112210.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PHACTR1	ENST00000332995.12	c.251-150162C>T		intron_variant		2	NM_030948.6	ENSP00000329880	P3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39900 AN: 151700 Hom.: 6161 Cov.: 31

Gnomad AFR AF: 0.129

Gnomad AMI AF: 0.441

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.384

Gnomad EAS AF: 0.0145

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.340

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.263 AC: 39908 AN: 151818 Hom.: 6169 Cov.: 31 AF XY: 0.259 AC XY: 19213 AN XY: 74198

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.384

Gnomad4 EAS AF: 0.0147

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.340

Gnomad4 OTH AF: 0.295

Alfa AF: 0.161 Hom.: 356

Bravo AF: 0.262

Asia WGS AF: 0.109 AC: 383 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.69
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4714955; hg19: chr6-12903435;