rs7957589

Positions:

• chr12-41480480-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.844-25976A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,138 control chromosomes in the GnomAD database, including 1,707 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 0.15 (1707 hom., cov: 32)
• Consequence: PDZRN4 NM_001164595.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.549

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PDZRN4	NM_001164595.2	c.844-25976A>T		intron_variant		ENST00000402685.7	NP_001158067.1
PDZRN4	NM_013377.4	c.70-25976A>T		intron_variant			NP_037509.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PDZRN4	ENST00000402685.7	c.844-25976A>T		intron_variant		2	NM_001164595.2	ENSP00000384197	P1
PDZRN4	ENST00000539469.6	c.70-25976A>T		intron_variant		1		ENSP00000439990
PDZRN4	ENST00000298919.7	c.63+2560A>T		intron_variant		2		ENSP00000298919
PDZRN4	ENST00000649474.1	c.-124+20410A>T		intron_variant				ENSP00000497437

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22233 AN: 152020 Hom.: 1705 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.149

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.154

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

GnomAD4 genome AF: 0.146 AC: 22227 AN: 152138 Hom.: 1707 Cov.: 32 AF XY: 0.146 AC XY: 10827 AN XY: 74378

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.198

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.154

Gnomad4 OTH AF: 0.152

Alfa AF: 0.142 Hom.: 186

Bravo AF: 0.141

Asia WGS AF: 0.157 AC: 546 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.7
DANN	Benign	0.72

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: rs7957589; hg19: chr12-41874282;