rs2305778

Positions:

• chr19-13933474-G-A

Variant summary

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

The NM_001370095.3(PODNL1):​c.768-19C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0699 in 1,533,248 control chromosomes in the GnomAD database, including 4,235 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 0.056 (304 hom., cov: 33)
  • Exomes 𝑓: 0.071 (3931 hom.)
• Consequence: PODNL1 NM_001370095.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219

Genes affected

PODNL1 (HGNC:26275): (podocan like 1) Predicted to be located in collagen-containing extracellular matrix. Predicted to be active in extracellular space. [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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PODNL1	NM_001370095.3	c.768-19C>T		intron_variant		ENST00000588872.3	NP_001357024.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PODNL1	ENST00000588872.3	c.768-19C>T		intron_variant		3	NM_001370095.3	ENSP00000467395	P1

Frequencies

GnomAD3 genomes AF: 0.0561 AC: 8530 AN: 152116 Hom.: 304 Cov.: 33

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.0571

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.108

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0905

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0674

Gnomad OTH AF: 0.0604

GnomAD3 exomes AF: 0.0772 AC: 14611 AN: 189162 Hom.: 680 AF XY: 0.0818 AC XY: 8384 AN XY: 102512

Gnomad AFR exome AF: 0.0100

Gnomad AMR exome AF: 0.0501

Gnomad ASJ exome AF: 0.126

Gnomad EAS exome AF: 0.110

Gnomad SAS exome AF: 0.144

Gnomad FIN exome AF: 0.0956

Gnomad NFE exome AF: 0.0697

Gnomad OTH exome AF: 0.0828

GnomAD4 exome AF: 0.0715 AC: 98690 AN: 1381014 Hom.: 3931 Cov.: 31 AF XY: 0.0735 AC XY: 49899 AN XY: 678834

Gnomad4 AFR exome AF: 0.0115

Gnomad4 AMR exome AF: 0.0494

Gnomad4 ASJ exome AF: 0.112

Gnomad4 EAS exome AF: 0.108

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.0949

Gnomad4 NFE exome AF: 0.0666

Gnomad4 OTH exome AF: 0.0732

GnomAD4 genome AF: 0.0560 AC: 8530 AN: 152234 Hom.: 304 Cov.: 33 AF XY: 0.0582 AC XY: 4330 AN XY: 74434

Gnomad4 AFR AF: 0.0114

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.108

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.0905

Gnomad4 NFE AF: 0.0674

Gnomad4 OTH AF: 0.0617

Alfa AF: 0.0681 Hom.: 565

Bravo AF: 0.0496

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2305778; hg19: chr19-14044287; COSMIC: COSV54308441; COSMIC: COSV54308441;