rs1458175

chr12-41572059-A-Cchr12-41572059-A-Gchr12-41572059-A-T

Variant summary

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

The NM_001164595.2(PDZRN4):c.1585-305A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.593 in 151,970 control chromosomes in the GnomAD database, including 27,390 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 0.59 (27390 hom., cov: 32)
• Consequence: PDZRN4 NM_001164595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896

Genes affected

PDZRN4 (HGNC:30552): (PDZ domain containing ring finger 4) Predicted to enable metal ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PDZRN4	NM_001164595.2	c.1585-305A>C		intron_variant		ENST00000402685.7
PDZRN4	NM_013377.4	c.811-305A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PDZRN4	ENST00000402685.7	c.1585-305A>C		intron_variant		2	NM_001164595.2	P1

Frequencies

GnomAD3 genomes AF: 0.593 AC: 90002 AN: 151852 Hom.: 27352 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.622

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.839

Gnomad SAS AF: 0.664

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.554

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.597

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

GnomAD4 genome AF: 0.593 AC: 90097 AN: 151970 Hom.: 27390 Cov.: 32 AF XY: 0.601 AC XY: 44642 AN XY: 74270

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.569

Gnomad4 EAS AF: 0.839

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.621

Gnomad4 NFE AF: 0.508

Gnomad4 OTH AF: 0.601

Alfa AF: 0.535 Hom.: 43760

Bravo AF: 0.598

Asia WGS AF: 0.756 AC: 2625 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
Cadd	Benign	0.24
Dann	Benign	0.69

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: rs1458175; hg19: chr12-41965861; COSMIC: COSV54204724;