5-37828202-C-T

Position:

• chr5-37828202-C-T

Variant summary

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

The NM_000514.4(GDNF):​c.151+6444G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 152,138 control chromosomes in the GnomAD database, including 42,002 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 0.74 (42002 hom., cov: 32)
• Consequence: GDNF NM_000514.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.646

Genes affected

GDNF (HGNC:4232): (glial cell derived neurotrophic factor) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate each subunit of the disulfide-linked homodimer. The recombinant form of this protein, a highly conserved neurotrophic factor, was shown to promote the survival and differentiation of dopaminergic neurons in culture, and was able to prevent apoptosis of motor neurons induced by axotomy. This protein is a ligand for the product of the RET (rearranged during transfection) protooncogene. Mutations in this gene may be associated with Hirschsprung disease and Tourette syndrome. This gene encodes multiple protein isoforms that may undergo similar proteolytic processing. [provided by RefSeq, Aug 2016]

GDNF-AS1 (HGNC:43592): (GDNF antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.784 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GDNF	NM_000514.4	c.151+6444G>A		intron_variant		ENST00000326524.7	NP_000505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GDNF	ENST00000326524.7	c.151+6444G>A		intron_variant		1	NM_000514.4	ENSP00000317145	P1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112924 AN: 152020 Hom.: 41961 Cov.: 32

Gnomad AFR AF: 0.725

Gnomad AMI AF: 0.720

Gnomad AMR AF: 0.767

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.661

Gnomad SAS AF: 0.805

Gnomad FIN AF: 0.782

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.746

Gnomad OTH AF: 0.725

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

GnomAD4 genome AF: 0.743 AC: 113013 AN: 152138 Hom.: 42002 Cov.: 32 AF XY: 0.745 AC XY: 55406 AN XY: 74380

Gnomad4 AFR AF: 0.725

Gnomad4 AMR AF: 0.767

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.661

Gnomad4 SAS AF: 0.805

Gnomad4 FIN AF: 0.782

Gnomad4 NFE AF: 0.746

Gnomad4 OTH AF: 0.720

Alfa AF: 0.741 Hom.: 5641

Bravo AF: 0.737

Asia WGS AF: 0.742 AC: 2583 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.12
DANN	Benign	0.45

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: rs2910702; hg19: chr5-37828304;