chr4-94567931-A-G

Variant names:

• chr4-94567931-A-G
• rs2452594
• NM_006457.5:c.249-5420A>G

Variant summary

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

The NM_006457.5(PDLIM5):​c.249-5420A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,130 control chromosomes in the GnomAD database, including 38,413 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 0.69 (38413 hom., cov: 32)
• Consequence: PDLIM5 NM_006457.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0930
• Publications: 4 publications found

Genes affected

PDLIM5 (HGNC:17468): (PDZ and LIM domain 5) This gene encodes a member of a family of proteins that possess a 100-amino acid PDZ domain at the N terminus and one to three LIM domains at the C-terminus. This family member functions as a scaffold protein that tethers protein kinases to the Z-disk in striated muscles. It is thought to function in cardiomyocyte expansion and in restraining postsynaptic growth of excitatory synapses. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jan 2012]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006457.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM5	NM_006457.5	MANE Select	c.249-5420A>G		intron	N/A	NP_006448.5
	PDLIM5	NM_001256426.2		c.249-5420A>G		intron	N/A	NP_001243355.2
	PDLIM5	NM_001011513.4		c.249-5420A>G		intron	N/A	NP_001011513.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDLIM5	ENST00000317968.9	TSL:1 MANE Select	c.249-5420A>G		intron	N/A	ENSP00000321746.4
	PDLIM5	ENST00000615540.4	TSL:1	c.249-5420A>G		intron	N/A	ENSP00000480359.1
	PDLIM5	ENST00000542407.5	TSL:1	c.249-5420A>G		intron	N/A	ENSP00000442187.2

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104682 AN: 152012 Hom.: 38407 Cov.: 32

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.697

Gnomad AMR AF: 0.758

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.900

Gnomad SAS AF: 0.897

Gnomad FIN AF: 0.855

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.778

Gnomad OTH AF: 0.711

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

GnomAD4 genome AF: 0.688 AC: 104715 AN: 152130 Hom.: 38413 Cov.: 32 AF XY: 0.699 AC XY: 52020 AN XY: 74378

African (AFR) AF: 0.408 AC: 16934 AN: 41466

American (AMR) AF: 0.759 AC: 11606 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2889 AN: 3466

East Asian (EAS) AF: 0.899 AC: 4652 AN: 5172

South Asian (SAS) AF: 0.897 AC: 4326 AN: 4824

European-Finnish (FIN) AF: 0.855 AC: 9063 AN: 10598

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.778 AC: 52874 AN: 67994

Other (OTH) AF: 0.713 AC: 1505 AN: 2110

Alfa AF: 0.759 Hom.: 22898

Bravo AF: 0.669

Asia WGS AF: 0.853 AC: 2964 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.96
DANN	Benign	0.47
PhyloP100		-0.093
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: rs2452594; hg19: chr4-95489082;