chr19-13933474-G-A

Variant names:

• chr19-13933474-G-A
• rs2305778
• NM_001370095.3:c.768-19C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370095.3. 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
	PODNL1	NM_001370095.3	MANE Select	c.768-19C>T		intron	N/A	NP_001357024.2
	PODNL1	NM_001146254.2		c.783-19C>T		intron	N/A	NP_001139726.1
	PODNL1	NM_024825.5		c.768-19C>T		intron	N/A	NP_079101.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PODNL1	ENST00000588872.3	TSL:3 MANE Select	c.768-19C>T		intron	N/A	ENSP00000467395.2
	PODNL1	ENST00000339560.10	TSL:1	c.768-19C>T		intron	N/A	ENSP00000345175.5
	PODNL1	ENST00000538371.6	TSL:2	c.783-19C>T		intron	N/A	ENSP00000442553.1

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

GnomAD2 exomes AF: 0.0772 AC: 14611 AN: 189162 AF XY: 0.0818

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 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

African (AFR) AF: 0.0115 AC: 367 AN: 31800

American (AMR) AF: 0.0494 AC: 1809 AN: 36600

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 2473 AN: 22098

East Asian (EAS) AF: 0.108 AC: 4201 AN: 38846

South Asian (SAS) AF: 0.131 AC: 10054 AN: 76544

European-Finnish (FIN) AF: 0.0949 AC: 3552 AN: 37420

Middle Eastern (MID) AF: 0.0846 AC: 461 AN: 5448

European-Non Finnish (NFE) AF: 0.0666 AC: 71573 AN: 1074914

Other (OTH) AF: 0.0732 AC: 4200 AN: 57344

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

African (AFR) AF: 0.0114 AC: 475 AN: 41554

American (AMR) AF: 0.0511 AC: 782 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 369 AN: 3466

East Asian (EAS) AF: 0.108 AC: 557 AN: 5158

South Asian (SAS) AF: 0.125 AC: 603 AN: 4830

European-Finnish (FIN) AF: 0.0905 AC: 960 AN: 10610

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.0674 AC: 4582 AN: 68010

Other (OTH) AF: 0.0617 AC: 130 AN: 2108

Alfa AF: 0.0656 Hom.: 659

Bravo AF: 0.0496

Asia WGS AF: 0.0960 AC: 334 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.6
DANN	Benign	0.42
PhyloP100		0.22
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2305778; hg19: chr19-14044287; COSMIC: COSV54308441; COSMIC: COSV54308441;