chr1-53084515-C-T

Position:

• chr1-53084515-C-T

Variant summary

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

The NM_153703.5(PODN):​c.*30C>T variant causes a splice region, 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.866 in 152,144 control chromosomes in the GnomAD database, including 57,869 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.87 (57744 hom., cov: 29)
  • Exomes 𝑓: 0.96 (125 hom.)
• Consequence: PODN NM_153703.5 splice_region, 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.59

Genes affected

PODN (HGNC:23174): (podocan) The protein encoded by this gene is a member of the small leucine-rich repeat protein family and contains an amino terminal CX3CXCX7C cysteine-rich cluster followed by a leucine-rich repeat domain. Studies suggest that this protein could function to inhibit smooth muscle cell proliferation and migration following arterial injury. [provided by RefSeq, Jul 2016]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PODN	NM_153703.5	c.*30C>T		splice_region_variant, 3_prime_UTR_variant	11/11	ENST00000312553.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PODN	ENST00000312553.10	c.*30C>T		splice_region_variant, 3_prime_UTR_variant	11/11	1	NM_153703.5	A2
	ENST00000447867.1	n.368+620G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.866 AC: 131394 AN: 151752 Hom.: 57720 Cov.: 29

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.952

Gnomad AMR AF: 0.742

Gnomad ASJ AF: 0.971

Gnomad EAS AF: 0.741

Gnomad SAS AF: 0.902

Gnomad FIN AF: 0.953

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.890

GnomAD4 exome AF: 0.956 AC: 262 AN: 274 Hom.: 125 Cov.: 0 AF XY: 0.953 AC XY: 183 AN XY: 192

Gnomad4 AFR exome AF: 0.900

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.750

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.917

Gnomad4 NFE exome AF: 0.963

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.866 AC: 131466 AN: 151870 Hom.: 57744 Cov.: 29 AF XY: 0.863 AC XY: 64049 AN XY: 74220

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.741

Gnomad4 ASJ AF: 0.971

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.903

Gnomad4 FIN AF: 0.953

Gnomad4 NFE AF: 0.947

Gnomad4 OTH AF: 0.886

Alfa AF: 0.922 Hom.: 88689

Bravo AF: 0.843

Asia WGS AF: 0.785 AC: 2730 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.54
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs899974; hg19: chr1-53550187;