rs3748076

Variant names:

• chr6-143757963-G-A
• rs3748076
• NM_001100164.2:c.455-2438G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-143757963-G-A
• chr6-143757963-G-C

Variant summary

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

The NM_001100164.2(PHACTR2):​c.455-2438G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 131,398 control chromosomes in the GnomAD database, including 18,517 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 0.56 (18517 hom., cov: 26)
• Consequence: PHACTR2 NM_001100164.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00
• Publications: 1 publications found

Genes affected

PHACTR2 (HGNC:20956): (phosphatase and actin regulator 2) Predicted to enable actin binding activity. Predicted to be involved in actin cytoskeleton organization. Predicted to be located in plasma membrane and platelet alpha granule membrane. Implicated in Parkinson's disease and multiple sclerosis. Biomarker of Alzheimer's disease. [provided by Alliance of Genome Resources, Apr 2022]

PHACTR2 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PHACTR2	NM_001100164.2	c.455-2438G>A		intron_variant	Intron 4 of 12	ENST00000440869.7	NP_001093634.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PHACTR2	ENST00000440869.7	c.455-2438G>A		intron_variant	Intron 4 of 12	2	NM_001100164.2	ENSP00000417038.2

Frequencies

GnomAD3 genomes AF: 0.565 AC: 74135 AN: 131322 Hom.: 18491 Cov.: 26

Gnomad AFR AF: 0.494

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.581

Gnomad ASJ AF: 0.549

Gnomad EAS AF: 0.576

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.588

Gnomad MID AF: 0.565

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.553

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

GnomAD4 genome AF: 0.565 AC: 74202 AN: 131398 Hom.: 18517 Cov.: 26 AF XY: 0.567 AC XY: 36498 AN XY: 64412

African (AFR) AF: 0.494 AC: 16216 AN: 32798

American (AMR) AF: 0.582 AC: 7994 AN: 13746

Ashkenazi Jewish (ASJ) AF: 0.549 AC: 1702 AN: 3100

East Asian (EAS) AF: 0.576 AC: 2762 AN: 4792

South Asian (SAS) AF: 0.633 AC: 2713 AN: 4288

European-Finnish (FIN) AF: 0.588 AC: 5591 AN: 9506

Middle Eastern (MID) AF: 0.561 AC: 137 AN: 244

European-Non Finnish (NFE) AF: 0.591 AC: 35614 AN: 60274

Other (OTH) AF: 0.558 AC: 1017 AN: 1824

Alfa AF: 0.459 Hom.: 1061

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.63
PhyloP100		0.0
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: rs3748076; hg19: chr6-144079100;